|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Commentary |
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
Author for correspondence (e-mail: haowu{at}med.cornell.edu )
 |
Summary |
|---|
 Top Summary IntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
Key words: TRAF, TNF, IL-1R/TLR, NF-
B, AP-1
|
Introduction |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
)), as well as in other multicellular organisms such as
Drosophila (Liu et al.,
1999; Grech et al.,
2000; Medzhitov and Janeway,
2000; Zapata et al.,
2000, Zapata et al.,
2000), Caenorhabditis elegans
(Wajant et al., 1998) and
Dictyostelium discoideum (Regnier
et al., 1995). Mammalian TRAFs have emerged as the major signal
transducers for the TNF receptor superfamily and the interleukin-1
receptor/Toll-like receptor (IL-1R/TLR) superfamily
(Table 1). A wide range of
biological functions, such as adaptive and innate immunity, embryonic
development, stress response and bone metabolism, are mediated by TRAFs
through the induction of cell survival, proliferation, differentiation and
death. TRAFs are also involved in the signal transduction of the Epstein-Barr
virus transforming protein LMP-1 (Mosialos
et al., 1995). In Drosophila, TRAFs are essential for
dorsoventral polarization and innate host defense by the signal transduction
initiated through the Toll receptor (Imler
and Hoffmann, 2001; Preiss et
al., 2001).
|
The TRAF proteins are characterized by the presence of a novel TRAF domain
at the C-terminus, which consists of a coiled-coil domain followed by a
conserved TRAF-C domain (Rothe et al.,
1994) (Fig. 1). The
TRAF domain plays an important role in TRAF function by mediating
self-association and upstream interactions with receptors and other signaling
proteins (Takeuchi et al.,
1996). The N-terminal portion of most TRAF proteins contains a
RING finger and several zinc finger motifs, which are important for downstream
signaling events (Rothe et al.,
1995; Takeuchi et al.,
1996).
|
Many of the biological effects of TRAF signaling appear to be mediated
through the activation of transcription factors of the NF-B and AP-1
family. NF-B promotes the expression of genes involved in inflammatory
and anti-apoptotic responses (Baeuerle and
Baltimore, 1996; Beg and
Baltimore, 1996; Liu et al.,
1996). It is activated by the IB kinase (IKK), which
consists of two kinase subunits, IKK
and IKKß, and a regulatory
subunit, IKK
/NEMO (DiDonato et al.,
1997; Regnier et al.,
1997; Zandi et al.,
1997; Krappmann et al.,
2000). Phosphorylation and degradation of IB lead to the
release and translocation of NF-B to the nucleus to activate
transcription (Stancovski and Baltimore,
1997). AP-1 activity is stimulated by mitogen-activated protein
(MAP) kinases through either direct phosphorylation or transcription of AP-1
components (Karin, 1996). MAP
kinases, which include Ser/Thr kinases such as JNKs/SAPKs, ERKs and p38s, are
at the downstream end of a three-tiered system that also contains MAP kinase
kinase (MAP2K) and MAP kinase kinase kinase (MAP3K). The stimulation of AP-1
activity by MAP kinases may elicit stress responses and promote both cell
survival and cell death (Shaulian and
Karin, 2001).
As adapter proteins, TRAFs elaborate receptor signal transduction by
serving as both a convergent and a divergent platform. Therefore, different
TRAFs are created with their own specific biological roles. Their distinct
upstream and downstream signaling pathways may determine this specificity.
Recent structural and biochemical data have provided us with a much better
understanding of the upstream signaling mechanism of TRAFs. Many of the
current studies of TRAF downstream signaling focus on the activation of
NF-B and AP-1 transcription factors. However, accumulating evidence
points to the differential regulation of this apparently common downstream
pathway as well as to additional TRAF-specific pathways for eliciting
different biological functions. We further suggest that signaling-dependent
TRAF trafficking may be another crucial regulatory factor. This commentary
will focus on the common and distinct molecular mechanisms of TRAF-mediated
signal transduction. For complementary information, please refer to other
recent reviews on TRAFs and TNF receptors
(Wallach et al., 1999;
Inoue et al., 2000;
Locksley et al., 2001;
Wajant et al., 2001).
|
Specific biological functions of mammalian TRAFs |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
). The other mammalian TRAFs were identified as follows: TRAF3
by its interaction with CD40 and the Epstein-Barr virus transforming protein
LMP1 (Cheng et al., 1995;
Mosialos et al., 1995;
Sato et al., 1995); TRAF4 by
its overexpression in breast carcinoma cells
(Regnier et al., 1995); TRAF5
by its interaction with CD40 and LTßR
(Ishida et al., 1996,
Ishida et al., 1996;
Nakano et al., 1996;
Mizushima et al., 1998) and
TRAF6 by its participation in the signal transduction of CD40 and
interleukin-1, a cytokine that is not related to TNF
(Cao et al., 1996b;
Ishida et al., 1996,
Ishida et al., 1996). However,
further extensive studies have shown that the specific biological function of
each TRAF protein is not necessarily related to its origin of identification
(Table 2,
Fig. 2).
|
|
Since its discovery, TRAF2 has become the prototypical member of the TRAF
family. The paradigm of TRAF-mediated NF-B and MAP kinase activation
was first demonstrated using both TRAF2 overexpression and a dominant-negative
phenotype of a TRAF2 derivative lacking the RING domain
(Rothe et al., 1995;
Hsu et al., 1996b;
Takeuchi et al., 1996;
Duckett et al., 1997;
Reinhard et al., 1997;
Arch et al., 1998). TRAF2
transcripts have been detected in almost every tissue
(Rothe et al., 1994), making
TRAF2 the most widely expressed TRAF family member.
TRAF2 plays a cytoprotective role, which was demonstrated by the premature
death of TRAF2-deficient mice owing to severe runting. In addition,
TRAF2-deficient cells are highly sensitive to TNF-induced cell death
(Yeh et al., 1997). The lack
of TRAF2 or the expression of a dominant-negative form of TRAF2 only led to a
modest defect in TNF-induced NF-B activation but resulted in a severe
reduction of JNK/SAPK activation (Lee et
al., 1997; Yeh et al.,
1997; Devin et al.,
2000). Recent data suggest that TRAF2 is important for NF-B
activation, but this role may be partially compensated for by the highly
related TRAF5 (see below) (Nakano et al.,
2000). The sensitization to TNF-induced cell death in the absence
of TRAF2 must have been largely due to an NF-B-independent mechanism
(Lee et al., 1997;
Yeh et al., 1997;
Lee et al., 1998). One
possibility may be related to the failure to recruit other proteins such as
cellular inhibitors of apoptosis proteins (cIAPs) to the TNFR1 receptor
signaling complex in the absence of TRAF2
(Wang et al., 1998;
Park et al., 2000). TNF
toxicity through TNFR1 appears to contribute significantly to the survival
defects in TRAF2-deficient mice because a double deficiency in TRAF2 and TNFR1
resulted in increased survival (Yeh et
al., 1999).
TRAF1, unlike TRAF2 and other TRAFs, does not have the N-terminal RING and
zinc-finger domains (Rothe et al.,
1994). TRAF1 expression is fairly restricted
(Rothe et al., 1994;
Mosialos et al., 1995) and can
be upregulated in lymphoid tumors and transformed lymphoid cells
(Durkop et al., 1999;
Zapata et al., 2000,
Zapata et al., 2000). The
current data are consistent with the idea that TRAF1 is an NF-B
inducible protein that protects cells from apoptosis and plays a role in the
feedback regulation of receptor signaling
(Speiser et al., 1997;
Wang et al., 1998;
Carpentier and Beyaert, 1999;
Schwenzer et al., 1999;
Nolan et al., 2000). It
appears that TRAF1 works in conjunction with TRAF2 and cIAPs to fully suppress
TNF-induced apoptosis. This may be achieved through the direct suppression of
caspase activation in the TNFR1 signaling complex by cIAPs, which are
specifically recruited through TRAF1 and TRAF2
(Wang et al., 1998;
Park et al., 2000).
Although TRAF3 possesses a putative domain organization similar to TRAF2
and TRAF5, overexpression of TRAF3 did not activate NF-B
(Rothe et al., 1995). In
contrast, it was reported that TRAF3 recruitment to LTßR led to cell
death (Force et al., 1997),
and that both N- and C-terminal domains of TRAF3 negatively regulate
NF-B activation induced by Ox40
(Takaori-Kondo et al., 2000).
However, it has also been shown that there are a variety of mRNA species of
TRAF3 and that some splice variants do induce NF-B activation
(van Eyndhoven et al., 1999).
Similar to TRAF2-deficient mice, TRAF3-deficient mice have poor perinatal and
neonatal survival (Xu et al.,
1996). However, despite the runting phenotype and the hypotrophy
of the spleen and thymus, which is similar to the phenotype displayed by
TRAF2-deficient mice, the immune system is fairly normal except in the
T-cell-dependent antigen responses (Xu et
al., 1996).
The biological importance of TRAF4 was revealed by the gross tracheal
malformation displayed by TRAF4-deficient mice
(Shiels et al., 2000), which
suggested a parallel function of TRAF4 with the Drosophila Toll
pathway in body organization. Analysis of TRAF4 expression has also implicated
TRAF4 in the function of neural multipotent cells and epithelial stem cells in
adult mammals (Krajewska et al.,
1998; Masson et al.,
1998). Even though there is evidence that TRAF4 may interact with
several receptors in the TNF receptor superfamily
(Krajewska et al., 1998;
Ye et al., 1999,
Ye et al., 1999), further
studies are required to elucidate the molecular pathway of TRAF4
signaling.
TRAF5 is considered to be a close functional and structural homologue of
TRAF2, and overexpression of TRAF5 can also activate NF-B and AP-1
transcription factors (Ishida et al.,
1996, Ishida et al.,
1996; Nakano et al.,
1996). However, deletion of TRAF5 did not cause perinatal
lethality, perhaps owing to the more restricted expression pattern of TRAF5
compared with TRAF2 (Ishida et al.,
1996, Ishida et al.,
1996; Nakano et al.,
1996). TRAF5 deficiency led to more specific defects in CD40- and
CD27-mediated lymphocyte activation, whereas TNF-mediated NF-B
activation was not severely affected
(Nakano et al., 1999).
Interestingly, TRAF2 and 5 double knockout animals did exhibit a severe
reduction in TNF-induced NF-B activation, which suggests that TRAF5 and
TRAF2 are partially functionally redundant
(Nakano et al., 2000).
TRAF6 possesses a unique receptor-binding specificity that results in its
crucial role as the signaling mediator for both the TNF receptor superfamily
and the IL-1R/TLR superfamily. As shown by targeted gene ablation, TRAF6 is
functionally important for both TRANCE-R-mediated osteoclast activation and
CD40 signaling (Lomaga et al.,
1999; Naito et al.,
1999; Wong et al., 1999b), even though both CD40 and TRANCE-R can
also signal through TRAF2 (Pullen et al.,
1998; Wong et al.,
1998). In the IL-1R/TLR superfamily, lack of TRAF6 leads to
defective signaling by IL-1 and IL-18 as well as hypo-responsiveness to
bacterial lipopolysaccharides (LPS), the cell wall component of Gram-negative
bacteria, which signals through TLR4
(Lomaga et al., 1999;
Naito et al., 1999). These
observations place TRAF6 as an important player in innate immunity against
pathogens.
The functional divergence of TRAFs appears to correlate well with a
proposed evolutionary relationship among TRAFs in mammals and other organisms
on the basis of sequence conservation in the TRAF domain and gene structure
analysis (Grech et al., 2000)
(Fig. 1). In this hypothesis,
TRAF4 and TRAF6 precursors appear to have arisen earlier in evolution. We
propose that TRAF4 and TRAF6 may be functional descendents of dTRAF1 and
dTRAF2, which have been implicated in Toll signal transduction
(Zapata et al., 2000,
Zapata et al., 2000;
Shen et al., 2001). This
argument points to the existence of a yet to be identified TRAF4-interacting
receptor. On the other hand, TRAF1, 2, 3 and 5 appear to be more recent
siblings in the TRAF family (Grech et al.,
2000). This observation is supported by the similar
receptor-binding specificity of these four TRAFs towards the TNF receptor
superfamily (see below) and the lack of known homologues of these receptors
beyond mammals.
|
Common and distinct signal transduction mechanisms up-stream of TRAFs |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
). There are at least three distinct ways that TRAF proteins
can be recruited to and activated by ligand-engaged receptors
(Fig. 2A). Members of the TNF
receptor superfamily that do not contain intracellular death domains, such as
TNFR2 and CD40, recruit TRAFs directly via short sequences in their
intracellular tails (Rothe et al.,
1994; Cheng et al.,
1995; Pullen et al.,
1998). Those that contain an intracellular death domain, such as
TNFR1, first recruit an adapter protein, TRADD, via a
death-domain—death-domain interaction
(Hsu et al., 1995). TRADD then
serves as a central platform of the TNFR1 signaling complex, which assembles
TRAF2 (Hsu et al., 1996b) and
RIP (Stanger et al., 1995;
Hsu et al., 1996a) for
survival signaling, and FADD and caspase-8 for the induction of apoptosis
(Hsu et al., 1996b). Members
of the IL-1R/TLR superfamily contain a protein interaction module known as the
TIR domain (Xu et al., 2000),
which recruits, sequentially, MyD88
(Wesche et al., 1997), a TIR
domain and death domain containing protein, and IRAKs
(Cao et al., 1996a;
Muzio et al., 1997;
Wesche et al., 1999), adapter
Ser/Thr kinases with death domains. IRAKs in turn associate with TRAF6 to
elicit signaling by IL-1 and pathogenic components such as LPS
(Cao et al., 1996b;
Zhang et al., 1999;
Hacker et al., 2000;
Wang et al., 2001,
Wang et al., 2001).
A common mechanism for the membrane-proximal event in TRAF signaling has
been revealed by the conserved trimeric association in the crystal structure
of the TRAF domain of TRAF2 (Park et al.,
1999; McWhirter et al.,
1999). The structure contains a stalk of a trimeric coiled-coil
and a cap of trimerized TRAF-C domain with a novel anti-parallel
ß-sandwich fold, leading to a prominent mushroom shaped structure
(Fig. 3A). This trimeric
stoichiometry of TRAFs provides a structural basis for signal transduction
across the cellular membrane after receptor trimerization by trimeric
extracellular ligands in the TNF superfamily
(Banner et al., 1993).
Interestingly, recent studies suggest that specific ligand-induced receptor
trimerization may be primed by non-signaling receptor pre-association prior to
ligand binding (Chan et al.,
2000; Siegel et al.,
2000). Thermodynamic characterization revealed the low affinity
nature of monomeric TRAF2-receptor interactions, which confirms the importance
of oligomerization-based affinity enhancement or avidity in receptor-mediated
TRAF recruitment (Ye and Wu,
2000).
|
Structural and biochemical studies have shown that a single TRAF protein
recognizes diverse receptor sequences via a conserved mode of interaction but
with a range of different affinities. In several different TRAF2 complexes,
receptor sequences bind invariably to the surface groove on the TRAF-C domain
of TRAF2 in an extended conformation, making main chain hydrogen bonding
interactions with the edge of the ß-sandwich structure
(Park et al., 1999;
McWhirter et al., 1999;
Ye et al., 1999,
Ye et al., 1999). The chain
direction of the receptor peptides allows the receptors to immediately latch
on to the TRAF-C domain after exiting from their transmembrane regions.
Although TRAF2-binding sequences from different receptors bear limited
sequence homology, their interactions with TRAF2 are preserved by a few
conserved structural contacts, as shown in the consensus (P/S/T/A)x(Q/E)E
(Ye et al., 1999,
Ye et al., 1999)
(Fig. 3B). A deviation from
this consensus, which bears the sequence of PxQxxD, is present in the human
Epstein-Barr virus LMP-1 protein and binds to the same surface of TRAF2 via
both similar and distinct features (Ye et
al., 1999, Ye et al.,
1999). Thermodynamic characterization further showed variable
affinities of TRAF2 with different receptor sequences, which are probably a
consequence of affinity modulations by non-conserved residues within and
beyond the core binding motif (Ye and Wu,
2000) (Table
3).
|
Further structural analyses have also revealed how several different TRAFs
can recognize a single receptor. The amino-acid residues on the TRAF2 surface
used for receptor interactions are conserved among TRAF1, 2, 3 and 5,
explaining the overlapping specificity of these TRAFs for different receptors
(Park et al., 1999;
Ye et al., 1999,
Ye et al., 1999). However, an
identical sequence from CD40 exhibits alternative binding modes to TRAF2 and
TRAF3, suggesting that this conserved interaction may vary to some extent in
different TRAFs, which modulates the strengths of the interactions
(Fig. 3C). In the TRAF3
complex, receptor residues distal to the central core sequence also interact
with TRAF3, leading to the formation of a hairpin on the TRAF3 surface, which
contributes strongly to TRAF3 interaction
(Ni et al., 2000).
The distinct mode of TRAF2 recruitment by TRADD was revealed by the crystal
structure of the TRAF2-TRADD complex (Park
et al., 2000) (Fig.
3D). The more extensive TRAF2-TRADD interface overlaps spatially
and therefore potentially competes with TRAF2-receptor interactions.
Biochemical characterization using surface plasmon resonance has shown that
the TRAF2-TRADD interaction is unique in two distinct ways. First, TRAF2 has a
significantly higher affinity for TRADD than for peptide motifs in direct
receptor interactions (Table
3), which leads to more efficient initiation of TRAF2 signaling by
TRADD. Second, TRADD has specificity for only TRAF1 and TRAF2, but not other
TRAF family members (Fig. 2A). It appears that TRAF1 and TRAF2 work in conjunction with associated caspase
inhibitors cIAPs to fully suppress TNF-induced apoptosis in the TNFR1
signaling complex (Wang et al.,
1998; Park et al.,
2000), leading to dominance of survival signaling for this
receptor under most circumstances.
TRAF6 directly interacts with CD40 and TRANCE-R, which are members of the
TNF receptor superfamily (Ishida et al.,
1996, Ishida et al.,
1996; Pullen et al.,
1998; Darnay et al.,
1999). For the signal transduction of the IL-1R/TLR superfamily,
TRAF6 is indirectly coupled to receptor activation via IRAK and the IRAK-TRAF6
pathway in evolutionarily analogous to the Pelle-dTRAF pathway in
Drosophila (Liu et al.,
1999; Zapata et al.,
2000, Zapata et al.,
2000; Shen et al.,
2001). Even though biochemical characterizations suggest that
TRAF6-receptor and TRAF6-IRAK interactions differ from receptor recognition by
other TRAFs (Pullen et al.,
1998; Darnay et al.,
1999), elucidation of the molecular mechanism of TRAF6 upstream
interactions awaits further structural information.
|
TRAF downstream signal transduction and regulation |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
B and AP-1 activation has been extensively studied
for the representative TRAF family members TRAF2 and TRAF6, which apparently
utilize different molecular pathways (Fig.
2B). Two models of TRAF2 downstream signaling pathways have been
proposed. The TRAF2-mediated NF-B activation may involve the direct
recruitment of the IKK complex in cooperation with RIP
(Yeh et al., 1997;
Kelliher et al., 1998;
Devin et al., 2000;
Nakano et al., 2000;
Zhang et al., 2000).
Furthermore, artificial oligomerization of either TRAF2 or RIP was sufficient
for NF-B activation (Baud et al.,
1999; Poyet et al.,
2000). Alternatively, TRAF2 can associate with several upstream
MAP kinases to induce NF-B and AP-1 activation. These include NIK
(Malinin et al., 1997;
Song et al., 1997), MEKK1 and
MEKK3 (Baud et al., 1999;
Yang et al., 2001) for IKK
activation and ASK1, MEKK1 and GCKR for initiating MAP kinase pathways and
AP-1 activation (Nishitoh et al.,
1998; Baud et al.,
1999; Hoeflich et al.,
1999; Shi et al.,
1999).
The activation of both NF-B and AP-1 by TRAF6 in the IL-1 signaling
pathway appears to involve a MAP3K known as TAK1
(Yamaguchi et al., 1995;
Ninomiya-Tsuji et al., 1999)
and two adapter proteins TAB1 (Shibuya et
al., 1996) and TAB2 (Takaesu
et al., 2000). Upon stimulation, TRAF6 associates with endogenous
TAK1 and TAB1 (Ninomiya-Tsuji et al.,
1999) and interacts with TAB2 following the translocation of TAB2
from the membrane to the cytosol (Takaesu
et al., 2001). Activated TAK1 appears to phosphorylate NIK, which
in turn activates IKK (Shirakabe et al.,
1997; Ninomiya-Tsuji et al.,
1999) and initiates the MAP kinase pathway. Surprisingly, it has
been shown recently that ubiquitination plays an important role in TAK1
activation (Deng et al., 2000;
Wang et al., 2001,
Wang et al., 2001). It
appears that as a RING-domain-containing protein, TRAF6 operates together with
a ubiquitin-conjugating enzyme system to catalyze the synthesis of unique
polyubiquitin chains essential for TRAF6 downstream signaling.
The ability of multiple TRAFs to activate NF-B and AP-1
transcription factors raises the question of how are the specific biological
functions of different TRAFs realized. We propose that the different signaling
pathways, such as those utilized by TRAF2 and TRAF6, may lead to preferential
activation of specific NF-B and AP-1 components and therefore the
transcription of an overlapping but non-identical set of genes. In addition,
many TRAF-interacting proteins have been identified and shown to regulate the
activation of NF-B and AP-1 in a TRAF-specific manner. For example, A20
is a TRAF1- and TRAF2-interacting protein
(Song et al., 1996) that
inhibits NF-B activation and regulates TNF-induced cell death responses
(Lee et al., 2000). A complete
review of these regulatory proteins is beyond the scope of this commentary;
however, their potential functions should not be overlooked.
A different level of regulation was revealed by several recent gene
knockout studies in which certain proteins were shown to regulate NF-B
transcriptional activity without affecting its DNA-binding activity. For
example, in mice deficient in the MAP3K NIK, normal NF-B DNA-binding
activity was observed upon treatment by a variety of cytokines, including TNF,
IL-1 and LTß. However, gene transcription upon LTßR activation was
selectively affected by the absence of NIK
(Yin et al., 2001).
Therefore, as different TRAFs may recruit a different set of these regulatory
proteins, their biological functions may be modulated by them.
In addition to NF-B and AP-1 activation, TRAF proteins have been
implicated in the crossover to additional signaling pathways. One such example
is TRAF6-mediated activation of Src family kinases. In osteoclasts at least,
TRAF6 plays an indispensable role in the activation of c-Src and subsequently
the anti-apoptotic kinase PKB/Akt (Coffer
et al., 1998; Wong et al., 1999a). Similarly, TRAF6-dependent
activation of another protein tyrosine kinase Syk has been shown to mediate
IL-1-induced chemokine production (Yamada
et al., 2001). Therefore, the differential regulation of
NF-B and AP-1, as well as the specific activation of other signaling
pathways, may collectively contribute to the specific functions of TRAFs.
|
Signaling-dependent TRAF trafficking |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
;
Hostager et al., 2000). Upon
receptor stimulation, TRAFs are redistributed to the cytoplasmic membrane or
to plasma membrane patches or caps
(Mosialos et al., 1995;
Kuhne et al., 1997). More
specifically, receptor recruitment of TRAFs during CD40 signaling could lead
to the partitioning of these TRAFs into membrane rafts, which are specific
regions of the plasma membrane that are rich in sphingolipid and cholesterol
(Hostager et al., 2000;
Vidalain et al., 2000). This
partitioning could be crucial for TRAF signaling as it physically stabilizes
the receptor signaling complexes and places TRAFs in the vicinity of a number
of signaling proteins including the Src family kinases, which are
preferentially localized in these membrane rafts. In fact, it has been found
that among the known TRAFs, the ability to redistribute to insoluble membrane
fractions consistently correlated with JNK activation. In addition, the forced
localization of TRAF3 to the cell membrane was sufficient to convert this
molecule into an activator of JNK
(Dadgostar and Cheng,
2000).
Although the redistribution of TRAFs into membrane fractions may lead to a
more sustained signaling of the activated receptor, it could also lead to a
depletion of cytoplasmic TRAFs and therefore downregulate subsequent
TRAF-dependent signal transduction (Arch et
al., 2000). Some TRAFs can accumulate in perinuclear compartments
after a particular signaling event (Arch et
al., 2000; Force et al.,
2000) but the eventual fate of these TRAFs is not clear. One
possibility is proteasome-dependent TRAF degradation
(Duckett and Thompson, 1997;
Brown et al., 2001), which
would limit the recycling of TRAFs for further signal transduction.
Interestingly, several TRAFs have been shown to interact with proteins of the
cytoskeleton and/or of particular membranes. These include the p62
nucleoporin, a component of the nuclear pore central plug
(Gamper et al., 2000), the
membrane-organizing protein caveolin-1
(Feng et al., 2001), the
microtubule-binding protein MIP-T3 (Ling
and Goeddel, 2000) and filamin
(Leonardi et al., 2000).
Clearly, this is an important field that requires further exploration and may
hold many of the clues to the specificity of TRAF-mediated signal
transduction.
|
Perspectives |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
|
Acknowledgments |
|---|
|
References |
|---|
|
TopSummaryIntroductionSpecific biological functions of...Common and distinct signal...TRAF downstream signal...Signaling-dependent TRAF...PerspectivesReferences |
|---|
Arch, R. H., Gedrich, R. W. and Thompson, C. B.
(1998). Tumor necrosis factor receptor-associated factors (TRAFs)
— a family of adapter proteins that regulates life and death.
Genes. Dev. 12,2821
-2830.
Arch, R. H., Gedrich, R. W. and Thompson, C. B. (2000). Translocation of TRAF proteins regulates apoptotic threshold of cells. Biochem. Biophys. Res. Commun. 272,936 -945.[Medline]
Baeuerle, P. A. and Baltimore, D. (1996). NF-kappa B: ten years after. Cell 87, 13-20.[Medline]
Banner, D. W., D'Arcy, A., Janes, W., Gentz, R., Schoenfeld, H. J., Broger, C., Loetscher, H. and Lesslauer, W. (1993). Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell 73,431 -445.[Medline]
Baud, V., Liu, Z. G., Bennett, B., Suzuki, N., Xia, Y. and
Karin, M. (1999). Signaling by proinflammatory cytokines:
oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation
and target gene induction via an amino-terminal effector domain.
Genes. Dev. 13,1297
-1308.
Beg, A. A. and Baltimore, D. (1996). An
essential role for NF-kappaB in preventing TNF-alpha-induced cell death.
Science 274,782
-784.
Brown, K. D., Hostager, B. S. and Bishop, G. A.
(2001). Differential signaling and tumor necrosis factor
receptor-associated factor (TRAF) degradation mediated by CD40 and the
Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1). J.
Exp. Med. 193,943
-954.
Cao, Z., Henzel, W. J. and Gao, X. (1996a). IRAK: A kinase associated with the interleukin-1 receptor. Science 271,1128 -1131.[Abstract]
Cao, Z., Xiong, J., Takeuchi, M., Kurama, T. and Goeddel, D. V. (1996b). TRAF6 is a signal transducer for interleukin-1. Nature 383,443 -446.[Medline]
Carpentier, I. and Beyaert, R. (1999). TRAF1 is a TNF inducible regulator of NF-kappaB activation. FEBS Lett. 460,246 -250.[Medline]
Chan, F. K., Chun, H. J., Zheng, L., Siegel, R. M., Bui, K. L.
and Lenardo, M. J. (2000). A domain in TNF receptors that
mediates ligand-independent receptor assembly and signaling.
Science 288,2351
-2354.
Cheng, G., Cleary, A. M., Ye, Z. S., Hong, D. I., Lederman, S.
and Baltimore, D. (1995). Involvement of CRAF1, a relative of
TRAF, in CD40 signaling. Science
267,1494
-1498.
Coffer, P. J., Jin, J. and Woodgett, J. R. (1998). Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem. J. 335, 1-13.
Dadgostar, H. and Cheng, G. (2000). Membrane
localization of TRAF 3 enables JNK activation. J. Biol.
Chem. 275,2539
-2544.
Darnay, B. G., Ni, J., Moore, P. A. and Aggarwal, B. B.
(1999). Activation of NF-kappaB by RANK requires tumor necrosis
factor receptor- associated factor (TRAF) 6 and NF-kappaB-inducing kinase.
Identification of a novel TRAF6 interaction motif. J. Biol.
Chem. 274,7724
-7731.
Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C. and Chen, Z. J. (2000). Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103,351 -361.[Medline]
Devin, A., Cook, A., Lin, Y., Rodriguez, Y., Kelliher, M. and Liu, Z. (2000). The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity 12,419 -429.[Medline]
DiDonato, J. A., Hayakawa, M., Rothward, D. M., Zandi, E. and Karin, M. (1997). A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388,548 -554.[Medline]
Duckett, C. S. and Thompson, C. B. (1997).
CD30-dependent degradation of TRAF2: implications for negative regulation of
TRAF signaling and the control of cell survival. Genes.
Dev. 11,2810
-2821.
Duckett, C. S., Gedrich, R. W., Gilfillan, M. C. and Thompson, C. B. (1997). Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol. Cell. Biol. 17,1535 -1542.[Abstract]
Durkop, H., Foss, H. D., Demel, G., Klotzbach, H., Hahn, C. and
Stein, H. (1999). Tumor necrosis factor receptor-associated
factor 1 is overexpressed in Reed-Sternberg cells of Hodgkin's disease and
Epstein-Barr virus-transformed lymphoid cells. Blood
93,617
-623.
Feng, X., Gaeta, M. L., Madge, L. A., Yang, J. H., Bradley, J.
R. and Pober, J. S. (2001). Caveolin-1 associates with TRAF2
to form a complex that is recruited to tumor necrosis factor receptors.
J. Biol. Chem. 276,8341
-8349.
Force, W. R., Cheung, T. C. and Ware, C. F.
(1997). Dominant negative mutants of TRAF3 reveal an important
role for the coiled coil domains in cell death signaling by the
lymphotoxin-beta receptor. J. Biol. Chem.
272,30835
-30840.
Force, W. R., Glass, A. A., Benedict, C. A., Cheung, T. C.,
Lama, J. and Ware, C. F. (2000). Discrete signaling regions
in the lymphotoxin-beta receptor for tumor necrosis factor receptor-associated
factor binding, subcellular localization, and activation of cell death and
NF-kappaB pathways. J. Biol. Chem.
275,11121
-11129.
Gamper, C., van Eyndhoven, W. G., Schweiger, E., Mossbacher, M., Koo, B. and Lederman, S. (2000). TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes. Mol. Immunol. 37, 73-84.[Medline]
Grech, A., Quinn, R., Srinivasan, D., Badoux, X. and Brink, R. (2000). Complete structural characterisation of the mammalian and Drosophila TRAF genes: implications for TRAF evolution and the role of RING finger splice variants. Mol. Immunol. 37,721 -734.[Medline]
Hacker, H., Vabulas, R. M., Takeuchi, O., Hoshino, K., Akira, S.
and Wagner, H. (2000). Immune cell activation by bacterial
CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor
receptor-associated factor (TRAF)6. J. Exp. Med.
192,595
-600.
Hoeflich, K. P., Yeh, W. C., Yao, Z., Mak, T. W. and Woodgett, J. R. (1999). Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1). Oncogene 18,5814 -5820.[Medline]
Hostager, B. S., Catlett, I. M. and Bishop, G. A.
(2000). Recruitment of CD40 and tumor necrosis factor
receptor-associated factors 2 and 3 to membrane microdomains during CD40
signaling. J. Biol. Chem.
275,15392
-15398.
Hsu, H., Huang, J., Shu, H. B., Baichwal, V. and Goeddel, D. V. (1996a). TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4, 387-396.[Medline]
Hsu, H., Shu, H.-B., Pan, M.-G. and Goeddel, D. V. (1996b). TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84,299 -308.[Medline]
Hsu, H., Xiong, J. and Goeddel, D. V. (1995). The TNF receptor 1-associated protein TRADD signals cell death and NF-kB activation. Cell 81,495 -504.[Medline]
Imler, J. L. and Hoffmann, J. A. (2001). Toll receptors in innate immunity. Trends Cell Biol. 11,304 -311.[Medline]
Inoue, J., Ishida, T., Tsukamoto, N., Kobayashi, N., Naito, A., Azuma, S. and Yamamoto, T. (2000). Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp. Cell Res. 254, 14-24.[Medline]
Ishida, T., Mizushima, S., Azuma, S., Kobayashi, N., Tojo, T.,
Suzuki, K., Aizawa, S., Watanabe, T., Mosialos, G., Kieff, E., Yamamoto, T.
and Inoue, J. (1996). Identification of TRAF6, a novel tumor
necrosis factor receptor-associated factor protein that mediates signaling
from an amino-terminal domain of the CD40 cytoplasmic region. J.
Biol. Chem. 271,28745
-28748.
Ishida, T. K., Tojo, T., Aoki, T., Kobayashi, N., Ohishi, T.,
Watanabe, T., Yamamoto, T. and Inoue, J. (1996). TRAF5, a
novel tumor necrosis factor receptor-associated factor family protein,
mediates CD40 signaling. Proc. Natl. Acad. Sci. USA
93,9437
-9442.
Karin, M. (1996). The regulation of AP-1 activity by mitogen-activated protein kinases. Philos. Trans. R. Soc. Lond. B Biol. Sci. 351,127 -134.[Medline]
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z. and Leder, P. (1998). The death-domain kinase RIP mediates the TNF-induced NF-kB signal. Immunity 8, 297-303.[Medline]
Krajewska, M., Krajewski, S., Zapata, J. M., Van Arsdale, T., Gascoyne, R. D., Berern, K., McFadden, D., Shabaik, A., Hugh, J., Reynolds, A., Clevenger, C. V. and Reed, J. C. (1998). TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. Am. J. Pathol. 152,1549 -1561.[Abstract]
Krappmann, D., Hatada, E. N., Tegethoff, S., Li, J., Klippel,
A., Giese, K., Baeuerle, P. A. and Scheidereit, C. (2000).
The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but
not IKAP as a regular component. J. Biol. Chem.
275,29779
-29787.
Kuhne, M. R., Robbins, M., Hambor, J. E., Mackey, M. F., Kosaka,
Y., Nishimura, T., Gigley, J. P., Noelle, R. J. and Calderhead, D. M.
(1997). Assembly and regulation of the CD40 receptor complex in
human B cells. J. Exp. Med.
186,337
-342.
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M.,
Lodolce, J. P. and Ma, A. (2000). Failure to regulate
TNF-induced NF-kappaB and cell death responses in A20-deficient mice.
Science 289,2350
-2354.
Lee, S. Y., Reichlin, A., Santana, A., Sokol, K. A., Nussenzweig, M. C. and Choi, Y. (1997). TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival. Immunity 7, 703-713.[Medline]
Lee, S. Y., Kaufman, D. R., Mora, A. L., Santana, A., Boothby,
M. and Choi, Y. (1998). Stimulus-dependent synergism of the
antiapoptotic tumor necrosis factor receptor-associated factor 2 (TRAF2) and
nuclear factor kappaB pathways. J. Exp. Med.
188,1381
-1384.
Leonardi, A., Ellinger-Ziegelbauer, H., Franzoso, G., Brown, K.
and Siebenlist, U. (2000). Physical and functional
interaction of filamin (actin-binding protein- 280) and tumor necrosis factor
receptor-associated factor 2. J. Biol. Chem.
275,271
-278.
Ling, L. and Goeddel, D. V. (2000). MIP-T3, a
novel protein linking tumor necrosis factor receptor- associated factor 3 to
the microtubule network. J. Biol. Chem.
275,23852
-23860.
Liu, Z. G., Hsu, H., Goeddel, D. V. and Karin, M.
(1996). Dissection of TNF receptor 1 effector functions: JNK
activation is not linked to apoptosis while NF-b activation prevents
cell death. Cell 87,565
-576.[Medline]
Liu, H., Su, Y. C., Becker, E., Treisman, J. and Skolnik, E. Y. (1999). A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. Curr. Biol. 9,101 -104.[Medline]
Locksley, R. M., Killeen, N. and Lenardo, M. J. (2001). The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104,487 -501.[Medline]
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger,
C., Ho, A., Morony, S., Capparelli, C., Van, G., Kaufman, S. et al.
(1999). TRAF6 deficiency results in osteopetrosis and defective
interleukin-1, CD40, and LPS signaling. Genes Dev.
13,1015
-1024.
Malinin, N. L., Boldin, M. P., Kovalenko, A. V. and Wallach,
D. (1997). MAP3K-related kinase involved in NF-B
induction by TNF, CD95 and IL-1. Nature
385,540
-544.[Medline]
Masson, R., Regnier, C. H., Chenard, M. P., Wendling, C., Mattei, M. G., Tomasetto, C. and Rio, M. C. (1998). Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development. Mech. Dev. 71,187 -191.[Medline]
McWhirter, S. M., Pullen, S. S., Holton, J. M., Crute, J. J.,
Kehry, M. R. and Alber, T. (1999). Crystallographic analysis
of CD40 recognition and signaling by human TRAF2. Proc. Natl. Acad.
Sci. USA 96,8408
-8413.
Medzhitov, R. and Janeway, C., Jr (2000). Innate immune recognition: mechanisms and pathways. Immunol. Rev. 173,89 -97.[Medline]
Mizushima, S., Fujita, M., Ishida, T., Azuma, S., Kato, K., Hirai, M., Otsuka, M., Yamamoto, T. and Inoue, J. (1998). Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5). Gene 207,135 -140.[Medline]
Mosialos, G., Birkenbach, M., Yalamanchili, R., VanArsdale, T., Ware, C. and Kieff, E. (1995). The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80,389 -399.[Medline]
Muzio, M., Ni, J., Feng, P. and Dixit, V. M.
(1997). IRAK (Pelle) family member IRAK-2 and MyD88 as proximal
mediators of IL-1 signaling. Science
278,1612
-1615.
Naito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., Nakao, K., Nakamura, K., Katsuki, M., Yamamoto, T. and Inoue, J. (1999). Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4,353 -362.[Abstract]
Nakano, H., Oshima, H., Chung, W., Williams-Abbott, L., Ware, C.
F., Yagita, H. and Okumura, K. (1996). TRAF5, an activator of
NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor.
J. Biol. Chem. 271,14661
-14664.
Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K.,
Matsumoto, M., Munechika, E., Sakai, T., Shirasawa, T., Akiba, H. et al.
(1999). Targeted disruption of Traf5 gene causes defects in CD40-
and CD27-mediated lymphocyte activation. Proc. Natl. Acad. Sci.
USA 96,9803
-9808.
Nakano, H., Kurosawa, K., Sakon, S., Yagita, H., Yeh, W. C., Mak, T. W. and Okumura, K. (2000). Impaired TNF-induced NF-kB activation and high sensitivity to TNF-induced cell death in TRAF2- and TRAF5-double deficient mice. Scand. J. Immuno. 51 (suppl 1),71 .
Ni, C. Z., Welsh, K., Leo, E., Chiou, C. K., Wu, H., Reed, J. C.
and Ely, K. R. (2000). Molecular basis for CD40 signaling
mediated by TRAF3. Proc. Natl. Acad. Sci. USA
97,10395
-10399.
Ninomiya-Tsuji, J., Kishimoto, K., Hiyama, A., Inoue, J., Cao, Z. and Matsumoto, K. (1999). The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398,252 -256.[Medline]
Nishitoh, H., Saitoh, M., Mochida, Y., Takeda, K., Nakano, H., Rothe, M., Miyazono, K. and Ichijo, H. (1998). ASK1 is essential for JNK/SAPK activation by TRAF2. Mol. Cell 2, 389-395.[Medline]
Nolan, B., Kim, R., Duffy, A., Sheth, K., De, M., Miller, C., Chari, R. and Bankey, P. (2000). Inhibited neutrophil apoptosis: proteasome dependent NF-kappaB translocation is required for TRAF-1 synthesis. Shock 14,290 -294.[Medline]
Park, Y. C., Burkitt, V., Villa, A. R., Tong, L. and Wu, H. (1999). Structural basis for self-association and receptor recognition of human TRAF2. Nature 398,533 -538.[Medline]
Park, Y. C., Ye, H., Hsia, C., Segal, D., Rich, R. L., Liou, H. C., Myszka, D. G. and Wu, H. (2000). A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101,777 -787.[Medline]
Poyet, J. L., Srinivasula, S. M., Lin, J. H., Fernandes-Alnemri,
T., Yamaoka, S., Tsichlis, P. N. and Alnemri, E. S. (2000).
Activation of the Ikappa B kinases by RIP via IKKgamma/NEMO-mediated
oligomerization. J. Biol. Chem.
275,37966
-37977.
Preiss, A., Johannes, B., Nagel, A. C., Maier, D., Peters, N. and Wajant, H. (2001). Dynamic expression of Drosophila TRAF1 during embryogenesis and larval development. Mech. Dev. 100,109 -113.[Medline]
Pullen, S. S., Miller, H. G., Everdeen, D. S., Dang, T. T., Crute, J. J. and Kehry, M. R. (1998). CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. Biochemistry 37,11836 -11845.[Medline]
Regnier, C. H., Tomasetto, C., Moog-Lutz, C., Chenard, M. P.,
Wendling, C., Basset, P. and Rio, M. C. (1995). Presence of a
new conserved domain in CART1, a novel member of the tumor necrosis factor
receptor-associated protein family, which is expressed in breast carcinoma.
J. Biol. Chem. 270,25715
-25721.
Regnier, C. H., Song, H. Y., Gao, X., Goeddel, D. V., Cao, Z. and Rothe, M. (1997). Identification and characterization of an IkappaB kinase. Cell 90,373 -383.[Medline]
Reinhard, C., Shamoon, B., Shyamala, V. and Williams, L. T. (1997). Tumor necrosis factor alpha-induced activation of c-jun N-terminal kinase is mediated by TRAF2. EMBO J. 16,1080 -1092.[Medline]
Rothe, M., Wong, S. C., Henzel, W. J. and Goeddel, D. V. (1994). A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78,681 -692.[Medline]
Rothe, M., Sarma, V., Dixit, V. M. and Goeddel, D. V.
(1995). TRAF2-mediated activation of NF-kappa B by TNF receptor 2
and CD40. Science 269,1424
-1427.
Sato, T., Irie, S. and Reed, J. C. (1995). A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Lett. 358,113 -118.[Medline]
Schwenzer, R., Siemienski, K., Liptay, S., Schubert, G., Peters,
N., Scheurich, P., Schmid, R. M. and Wajant, H. (1999). The
human tumor necrosis factor (TNF) receptor-associated factor 1 gene (TRAF1) is
upregulated by cytokines of the TNF ligand family and modulates TNF-induced
activation of NF-kappaB and c-Jun N-terminal kinase. J. Biol.
Chem. 274,19368
-19374.
Shaulian, E. and Karin, M. (2001). AP-1 in cell proliferation and survival. Oncogene 20,2390 -2400.[Medline]
Shen, B., Liu, H., Skolnik, E. Y. and Manley, J. L.
(2001). Physical and functional interactions between Drosophila
TRAF2 and Pelle kinase contribute to Dorsal activation. Proc. Natl.
Acad. Sci. USA 98,8596
-8601.
Shi, C. S., Leonardi, A., Kyriakis, J., Siebenlist, U. and
Kehrl, J. H. (1999). TNF-mediated activation of the
stress-activated protein kinase pathway: TNF receptor-associated factor 2
recruits and activates germinal center kinase related. J.
Immunol. 163,3279
-3285.
Shibuya, H., Yamaguchi, K., Shirakabe, K., Tonegawa, A., Gotoh, Y., Ueno, N., Irie, K., Nishida, E. and Matsumoto, K. (1996). TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science 272,1179 -1182.[Abstract]
Shiels, H., Li, X., Schumacker, P. T., Maltepe, E., Padrid, P.
A., Sperling, A., Thompson, C. B. and Lindsten, T. (2000).
TRAF4 deficiency leads to tracheal malformation with resulting alterations in
air flow to the lungs. Am. J. Pathol.
157,679
-688.
Shirakabe, K., Yamaguchi, K., Shibuya, H., Irie, K., Matsuda,
S., Moriguchi, T., Gotoh, Y., Matsumoto, K. and Nishida, E.
(1997). TAK1 mediates the ceramide signaling to stress-activated
protein kinase/c-Jun N-terminal kinase. J. Biol. Chem.
272,8141
-8144.
Siegel, R. M., Frederiksen, J. K., Zacharias, D. A., Chan, F.
K., Johnson, M., Lynch, D., Tsien, R. Y. and Lenardo, M. J.
(2000). Fas preassociation required for apoptosis signaling and
dominant inhibition by pathogenic mutations. Science
288,2354
-2357.
Song, H. Y., Rothe, M. and Goeddel, D. V.
(1996). The tumor necrosis factor-inducible zinc finger protein
A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation.
Proc. Natl. Acad. Sci. USA
93,6721
-6725.
Song, H. Y., Regnier, C. H., Kirschning, C. J., Goeddel, D. V.
and Rothe, M. (1997). Tumor necrosis factor (TNF)-mediated
kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal
kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2.
Proc. Natl. Acad. Sci. USA
94,9792
-9796.
Speiser, D. E., Lee, S. Y., Wong, B., Arron, J., Santana, A.,
Kong, Y. Y., Ohashi, P. S. and Choi, Y. (1997). A regulatory
role for TRAF1 in antigen-induced apoptosis of T cells. J. Exp.
Med. 185,1777
-1783.
Stancovski, I. and Baltimore, D. (1997). NF-kB activation: The IkB kinase revealed? Cell 91,299 -302.[Medline]
Stanger, B. Z., Leder, P., Lee, T., Kim, E. and Seed, B. (1995). RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81,513 -523.[Medline]
Takaesu, G., Kishida, S., Hiyama, A., Yamaguchi, K., Shibuya, H., Irie, K., Ninomiya-Tsuji, J. and Matsumoto, K. (2000). TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol. Cell 5,649 -658.[Medline]
Takaesu, G., Ninomiya-Tsuji, J., Kishida, S., Li, X., Stark, G.
R. and Matsumoto, K. (2001). Interleukin-1 (IL-1)
receptor-associated kinase leads to activation of TAK1 by inducing TAB2
translocation in the IL-1 signaling pathway. Mol. Cell
Biol. 21,2475
-2484.
Takaori-Kondo, A., Hori, T., Fukunaga, K., Morita, R., Kawamata, S. and Uchiyama, T. (2000). Both amino- and carboxyl-terminal domains of TRAF3 negatively regulate NF-kappaB activation induced by OX40 signaling. Biochem. Biophys. Res. Commun. 272,856 -863.[Medline]
Takeuchi, M., Rothe, M. and Goeddel, D. V.
(1996). Anatomy of TRAF2. Distinct domains for nuclear
factor-kappaB activation and association with tumor necrosis factor signaling
proteins. J. Biol. Chem.
271,19935
-19942.
van Eyndhoven, W. G., Gamper, C. J., Cho, E., Mackus, W. J. and Lederman, S. (1999). TRAF-3 mRNA splice-deletion variants encode isoforms that induce NF- kappaB activation. Mol. Immunol. 36,647 -658.[Medline]
Vidalain, P. O., Azocar, O., Servet-Delprat, C., Rabourdin-Combe, C., Gerlier, D. and Manie, S. (2000). CD40 signaling in human dendritic cells is initiated within membrane rafts. EMBO J. 19,3304 -3313.[Medline]
Wallach, D., Varfolomeev, E. E., Malinin, N. L., Goltsev, Y. V., Kovalenko, A. V. and Boldin, M. P. (1999). Tumor necrosis factor receptor and Fas signaling mechanisms. Annu. Rev. Immunol. 17,331 -367.[Medline]
Wajant, H., Muhlenbeck, F. and Scheurich, P. (1998). Identification of a TRAF (TNF receptor-associated factor) gene in Caenorhabditis elegans. J. Mol. Evol. 47,656 -662.[Medline]
Wajant, H., Henkler, F. and Scheurich, P. (2001). The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal. 13,389 -400.[Medline]
Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J. and Chen, Z. J. (2001). TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412,346 -351.[Medline]
Wang, C. Y., Mayo, M. W., Korneluk, R. G., Goeddel, D. V. and
Baldwin, A. S., Jr (1998). NF-kappaB antiapoptosis: induction
of TRAF1 and TRAF2 and c-IAP1 and c- IAP2 to suppress caspase-8 activation.
Science 281,1680
-1683.
Wang, Q., Dziarski, R., Kirschning, C. J., Muzio, M. and Gupta,
D. (2001). Micrococci and peptidoglycan activate
TLR2->MyD88->IRAK->TRAF->NIK->IKK->NF-kappaB signal
transduction pathway that induces transcription of interleukin-8.
Infect. Immun. 69,2270
-2276.
Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S. and Cao, Z. (1997). MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7, 837-847.[Medline]
Wesche, H., Gao, X., Li, X., Kirschning, C. J., Stark, G. R. and
Cao, Z. (1999). IRAK-M is a novel member of the
Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J.
Biol. Chem. 274,19403
-19410.
Wong, B. R., Josien, R., Lee, S. Y., Vologodskaia, M., Steinman,
R. M. and Choi, Y. (1998). The TRAF family of signal
transducers mediates NF-kappaB activation by the TRANCE receptor.
J. Biol. Chem. 273,28355
-28359.
Wong, B. R., Besser, D., Kim, N., Arron, J. R., Vologodskaia, M., Hanafusa, H. and Choi, Y. (1999). TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol. Cell 4,1041 -1049.[Medline]
Wong, B. R., Josien, R. and Choi, Y. (1999). TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J. Leukoc. Biol. 65,715 -724.[Abstract]
Xu, Y., Cheng, G. and Baltimore, D. (1996). Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses. Immunity 5, 407-415.[Medline]
Xu, Y., Tao, X., Shen, B., Horng, T., Medzhitov, R., Manley, J. L. and Tong, L. (2000). Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408,111 -115.[Medline]
Yamada, T., Fujieda, S., Yanagi, S., Yamamura, H., Inatome, R.,
Yamamoto, H., Igawa, H. and Saito, H. (2001). Il-1 induced
chemokine production through the association of syk with tnf
receptor-associated factor-6 in nasal fibroblast lines. J
Immunol 167,283
-288.
Yamaguchi, K., Shirakabe, K., Shibuya, H., Irie, K., Oishi, I.,
Ueno, N., Taniguchi, T., Nishida, E. and Matsumoto, K.
(1995). Identification of a member of the MAPKKK family as a
potential mediator of TGF-beta signal transduction.
Science 270,2008
-2011.
Yang, J., Lin, Y., Guo, Z., Cheng, J., Huang, J., Deng, L., Liao, W., Chen, Z., Liu, Z. and Su, B. (2001). The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nat. Immunol. 2,620 -624.[Medline]
Ye, H., Park, Y. C., Kreishman, M., Kieff, E. and Wu, H. (1999). The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol. Cell 4, 321-330.[Medline]
Ye, H. and Wu, H. (2000). Thermodynamic
characterization of the interaction between TRAF2 and receptor peptides by
isothermal titration calorimetry. Proc. Natl. Acad. Sci.
USA 97,8961
-8966.
Ye, X., Mehlen, P., Rabizadeh, S., VanArsdale, T., Zhang, H.,
Shin, H., Wang, J. J., Leo, E., Zapata, J., Hauser, C. A., Reed, J. C. and
Bredesen, D. E. (1999). TRAF family proteins interact with
the common neurotrophin receptor and modulate apoptosis induction.
J. Biol. Chem. 274,30202
-30208.
Yeh, W. C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A., de la Pompa, J. L., Ferrick, D., Hum, B., Iscove, N., Ohashi, P., Rothe, M., Goeddel, D. V. and Mak, T. W. (1997). Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 7,715 -725.[Medline]
Yeh, W. C., Hakem, R., Woo, M. and Mak, T. W. (1999). Gene targeting in the analysis of mammalian apoptosis and TNF receptor superfamily signaling. Immunol. Rev. 169,283 -302.[Medline]
Yin, L., Wu, L., Wesche, H., Arthur, C. D., White, J. M.,
Goeddel, D. V. and Schreiber, R. D. (2001). Defective
lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in
NIK-deficient mice. Science
291,2162
-2165.
Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M. and Karin, M. (1997). The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 91,243 -252.[Medline]
Zapata, J. M., Krajewska, M., Krajewski, S., Kitada, S., Welsh,
K., Monks, A., McCloskey, N., Gordon, J., Kipps, T. J., Gascoyne, R. D.,
Shabaik, A. and Reed, J. C. (2000). TNFR-associated factor
family protein expression in normal tissues and lymphoid malignancies.
J. Immunol. 165,5084
-5096.
Zapata, J. M., Matsuzawa, S., Godzik, A., Leo, E., Wasserman, S.
A. and Reed, J. C. (2000). The Drosophila tumor
necrosis factor receptor-associated factor-1 (DTRAF1) interacts with Pelle and
regulates NFkappaB activity. J. Biol. Chem.
275,12102
-12107.
Zhang, F. X., Kirschning, C. J., Mancinelli, R., Xu, X. P., Jin,
Y., Faure, E., Mantovani, A., Rothe, M., Muzio, M. and Arditi, M.
(1999). Bacterial lipopolysaccharide activates nuclear
factor-kappaB through interleukin-1 signaling mediators in cultured human
dermal endothelial cells and mononuclear phagocytes. J. Biol.
Chem. 274,7611
-7614.
Zhang, S. Q., Kovalenko, A., Cantarella, G. and Wallach, D. (2000). Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity 12,301 -311.[Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  S. J. Mathew, D. Haubert, M. Kronke, and M. Leptin Looking beyond death: a morphogenetic role for the TNF signalling pathway J. Cell Sci., June 15, 2009; 122(12): 1939 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, S. Wang, P. Zhang, N. Said-Al-Naief, S. M. Michalek, and X. Feng Molecular Mechanism of the Bifunctional Role of Lipopolysaccharide in Osteoclastogenesis J. Biol. Chem., May 1, 2009; 284(18): 12512 - 12523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, A. Mittal, P. K. Paul, M. Kumar, D. S. Srivastava, S. C. Tyagi, and A. Kumar Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-{kappa}B-inducing Kinase and p38 Mitogen-activated Protein Kinase: A POTENTIAL ROLE OF MMP-9 IN MYOPATHY J. Biol. Chem., February 13, 2009; 284(7): 4439 - 4450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ning, A. D. Campos, B. G. Darnay, G. L. Bentz, and J. S. Pagano TRAF6 and the Three C-Terminal Lysine Sites on IRF7 Are Required for Its Ubiquitination-Mediated Activation by the Tumor Necrosis Factor Receptor Family Member Latent Membrane Protein 1 Mol. Cell. Biol., October 15, 2008; 28(20): 6536 - 6546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zheng, S. E. Morgan-Lappe, J. Yang, K. M. Bockbrader, D. Pamarthy, D. Thomas, S. W. Fesik, and Y. Sun Growth Inhibition and Radiosensitization of Glioblastoma and Lung Cancer Cells by Small Interfering RNA Silencing of Tumor Necrosis Factor Receptor-Associated Factor 2 Cancer Res., September 15, 2008; 68(18): 7570 - 7578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lamothe, A. D. Campos, W. K. Webster, A. Gopinathan, L. Hur, and B. G. Darnay The RING Domain and First Zinc Finger of TRAF6 Coordinate Signaling by Interleukin-1, Lipopolysaccharide, and RANKL J. Biol. Chem., September 5, 2008; 283(36): 24871 - 24880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Guarini, S. Chiaretti, S. Tavolaro, R. Maggio, N. Peragine, F. Citarella, M. R. Ricciardi, S. Santangelo, M. Marinelli, M. S. De Propris, et al. BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells Blood, August 1, 2008; 112(3): 782 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Huang, S. Yuan, L. Guo, Y. Yu, J. Li, T. Wu, T. Liu, M. Yang, K. Wu, H. Liu, et al. Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity Genome Res., July 1, 2008; 18(7): 1112 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sabbagh, G. Pulle, Y. Liu, E. N. Tsitsikov, and T. H. Watts ERK-Dependent Bim Modulation Downstream of the 4-1BB-TRAF1 Signaling Axis Is a Critical Mediator of CD8 T Cell Survival In Vivo J. Immunol., June 15, 2008; 180(12): 8093 - 8101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Yang, A. Murti, S. R. Pfeffer, M. Fan, Z. Du, and L. M. Pfeffer The Role of TRAF2 Binding to the Type I Interferon Receptor in Alternative NF{kappa}B Activation and Antiviral Response J. Biol. Chem., May 23, 2008; 283(21): 14309 - 14316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Machado, L. Esper, A. Dias, R. Madan, Y. Gu, D. Hildeman, C. N. Serhan, C. L. Karp, and J. Aliberti Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6 J. Exp. Med., May 12, 2008; 205(5): 1077 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Pham, H.-J. Zhou, Y.-C. Lin-Lee, A. T. Tamayo, L. C. Yoshimura, L. Fu, B. G. Darnay, and R. J. Ford Nuclear Tumor Necrosis Factor Receptor-associated Factor 6 in Lymphoid Cells Negatively Regulates c-Myb-mediated Transactivation through Small Ubiquitin-related Modifier-1 Modification J. Biol. Chem., February 22, 2008; 283(8): 5081 - 5089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Rowland, M. M. Tremblay, J. M. Ellison, L. L. Stunz, G. A. Bishop, and B. S. Hostager A Novel Mechanism for TNFR-Associated Factor 6-Dependent CD40 Signaling J. Immunol., October 1, 2007; 179(7): 4645 - 4653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Abbott, Y. Yang, J. E. Hutti, S. Madhavarapu, M. A. Kelliher, and L. C. Cantley Coordinated Regulation of Toll-Like Receptor and NOD2 Signaling by K63-Linked Polyubiquitin Chains Mol. Cell. Biol., September 1, 2007; 27(17): 6012 - 6025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Baguet, S. Degot, N. Cougot, E. Bertrand, M.-P. Chenard, C. Wendling, P. Kessler, H. Le Hir, M.-C. Rio, and C. Tomasetto The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly J. Cell Sci., August 15, 2007; 120(16): 2774 - 2784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Morriswood, G. Ryzhakov, C. Puri, S. D. Arden, R. Roberts, C. Dendrou, J. Kendrick-Jones, and F. Buss T6BP and NDP52 are myosin VI binding partners with potential roles in cytokine signalling and cell adhesion J. Cell Sci., August 1, 2007; 120(15): 2574 - 2585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Guo and G. Cheng Modulation of the Interferon Antiviral Response by the TBK1/IKKi Adaptor Protein TANK J. Biol. Chem., April 20, 2007; 282(16): 11817 - 11826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Garcia, J. Kaserman, Y.-H. Chung, J. U. Jung, and S.-H. Lee Herpesvirus Saimiri STP-A Oncoprotein Utilizes Src Family Protein Tyrosine Kinase and Tumor Necrosis Factor Receptor-Associated Factors To Elicit Cellular Signal Transduction J. Virol., March 15, 2007; 81(6): 2663 - 2674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-K. Min, Y.-L. Cho, J.-H. Choi, Y. Kim, J. H. Kim, Y. S. Yu, J. Rho, N. Mochizuki, Y.-M. Kim, G. T. Oh, et al. Receptor activator of nuclear factor (NF)-{kappa}B ligand (RANKL) increases vascular permeability: impaired permeability and angiogenesis in eNOS-deficient mice Blood, February 15, 2007; 109(4): 1495 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lamothe, A. Besse, A. D. Campos, W. K. Webster, H. Wu, and B. G. Darnay Site-specific Lys-63-linked Tumor Necrosis Factor Receptor-associated Factor 6 Auto-ubiquitination Is a Critical Determinant of I{kappa}B Kinase Activation J. Biol. Chem., February 9, 2007; 282(6): 4102 - 4112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Q. He, S. K. Saha, J. R. Kang, B. Zarnegar, and G. Cheng Specificity of TRAF3 in Its Negative Regulation of the Noncanonical NF-{kappa}B Pathway J. Biol. Chem., February 9, 2007; 282(6): 3688 - 3694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Garcia, J. Gil, I. Ventoso, S. Guerra, E. Domingo, C. Rivas, and M. Esteban Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1032 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Nagy, H. Rui, S. M. Stepkowski, J. Karras, and R. A. Kirken A Preferential Role for STAT5, not Constitutively Active STAT3, in Promoting Survival of a Human Lymphoid Tumor J. Immunol., October 15, 2006; 177(8): 5032 - 5040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Miggin and L. A. J. O'Neill New insights into the regulation of TLR signaling J. Leukoc. Biol., August 1, 2006; 80(2): 220 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Jarvis, J. A. Borton, A. M. Keech, J. Wong, W. J. Britt, B. E. Magun, and J. A. Nelson Human Cytomegalovirus Attenuates Interleukin-1{beta} and Tumor Necrosis Factor Alpha Proinflammatory Signaling by Inhibition of NF-{kappa}B Activation. J. Virol., June 1, 2006; 80(11): 5588 - 5598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. K. Misra, R. Deedwania, and S. V. Pizzo Activation and Cross-talk between Akt, NF-{kappa}B, and Unfolded Protein Response Signaling in 1-LN Prostate Cancer Cells Consequent to Ligation of Cell Surface-associated GRP78 J. Biol. Chem., May 12, 2006; 281(19): 13694 - 13707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xu, S. Wang, W. Liu, J. Liu, and X. Feng A Novel Receptor Activator of NF-{kappa}B (RANK) Cytoplasmic Motif Plays an Essential Role in Osteoclastogenesis by Committing Macrophages to the Osteoclast Lineage J. Biol. Chem., February 24, 2006; 281(8): 4678 - 4690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mauro, E. Crescenzi, R. De Mattia, F. Pacifico, S. Mellone, S. Salzano, C. de Luca, L. D'Adamio, G. Palumbo, S. Formisano, et al. Central Role of the Scaffold Protein Tumor Necrosis Factor Receptor-associated Factor 2 in Regulating Endoplasmic Reticulum Stress-induced Apoptosis J. Biol. Chem., February 3, 2006; 281(5): 2631 - 2638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wu, H. Nakano, and Z. Wu The C-terminal Activating Region 2 of the Epstein-Barr Virus-encoded Latent Membrane Protein 1 Activates NF-{kappa}B through TRAF6 and TAK1 J. Biol. Chem., January 27, 2006; 281(4): 2162 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wan, W. Zhang, L. Wu, T. Bai, M. Zhang, K.-w. Lo, Y.-l. Chui, Y. Cui, Q. Tao, M. Yamamoto, et al. BS69, a Specific Adaptor in the Latent Membrane Protein 1-Mediated c-Jun N-Terminal Kinase Pathway Mol. Cell. Biol., January 15, 2006; 26(2): 448 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. O. Nashar and J. R. Drake Dynamics of MHC Class II-Activating Signals in Murine Resting B Cells J. Immunol., January 15, 2006; 176(2): 827 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Maezawa, H. Nakajima, K. Suzuki, T. Tamachi, K. Ikeda, J.-i. Inoue, Y. Saito, and I. Iwamoto Involvement of TNF Receptor-Associated Factor 6 in IL-25 Receptor Signaling J. Immunol., January 15, 2006; 176(2): 1013 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A.F. Marteijn, L. van Emst, C. A.J. Erpelinck-Verschueren, G. Nikoloski, A. Menke, T. de Witte, B. Lowenberg, J. H. Jansen, and B. A. van der Reijden The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells Blood, December 15, 2005; 106(13): 4114 - 4123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rojas-Cartagena, C. B. Appleyard, O. I. Santiago, and I. Flores Experimental Intestinal Endometriosis Is Characterized by Increased Levels of Soluble TNFRSF1B and Downregulation of Tnfrsf1a and Tnfrsf1b Gene Expression Biol Reprod, December 1, 2005; 73(6): 1211 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Davies, T. W. Mak, L. S. Young, and A. G. Eliopoulos TRAF6 Is Required for TRAF2-Dependent CD40 Signal Transduction in Nonhemopoietic Cells Mol. Cell. Biol., November 15, 2005; 25(22): 9806 - 9819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Noguchi, K. Takeda, A. Matsuzawa, K. Saegusa, H. Nakano, J. Gohda, J.-i. Inoue, and H. Ichijo Recruitment of Tumor Necrosis Factor Receptor-associated Factor Family Proteins to Apoptosis Signal-regulating Kinase 1 Signalosome Is Essential for Oxidative Stress-induced Cell Death J. Biol. Chem., November 4, 2005; 280(44): 37033 - 37040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Andrade, M. Wessendarp, J.-A. C. Portillo, J.-Q. Yang, F. J. Gomez, J. E. Durbin, G. A. Bishop, and C. S. Subauste TNF Receptor-Associated Factor 6-Dependent CD40 Signaling Primes Macrophages to Acquire Antimicrobial Activity in Response to TNF-{alpha} J. Immunol., November 1, 2005; 175(9): 6014 - 6021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Abell and G. L. Johnson MEKK4 Is an Effector of the Embryonic TRAF4 for JNK Activation J. Biol. Chem., October 28, 2005; 280(43): 35793 - 35796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wu, P. Xie, K. Welsh, C. Li, C.-Z. Ni, X. Zhu, J. C. Reed, A. C. Satterthwait, G. A. Bishop, and K. R. Ely LMP1 Protein from the Epstein-Barr Virus Is a Structural CD40 Decoy in B Lymphocytes for Binding to TRAF3 J. Biol. Chem., September 30, 2005; 280(39): 33620 - 33626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-K. Min, Y.-M. Kim, S. W. Kim, M.-C. Kwon, Y.-Y. Kong, I. K. Hwang, M. H. Won, J. Rho, and Y.-G. Kwon TNF-Related Activation-Induced Cytokine Enhances Leukocyte Adhesiveness: Induction of ICAM-1 and VCAM-1 via TNF Receptor-Associated Factor and Protein Kinase C-Dependent NF-{kappa}B Activation in Endothelial Cells J. Immunol., July 1, 2005; 175(1): 531 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Das, J. Cho, I. Lambertz, M. A. Kelliher, A. G. Eliopoulos, K. Du, and P. N. Tsichlis Tpl2/Cot Signals Activate ERK, JNK, and NF-{kappa}B in a Cell-type and Stimulus-specific Manner J. Biol. Chem., June 24, 2005; 280(25): 23748 - 23757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Esparza and R. H. Arch Glucocorticoid-Induced TNF Receptor, a Costimulatory Receptor on Naive and Activated T Cells, Uses TNF Receptor-Associated Factor 2 in a Novel Fashion as an Inhibitor of NF-{kappa}B Activation J. Immunol., June 15, 2005; 174(12): 7875 - 7882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Y. Kim, G. Anderson, A. White, E. Jenkinson, W. Arlt, I.-L. Martensson, L. Erlandsson, and P. J. L. Lane OX40 Ligand and CD30 Ligand Are Expressed on Adult but Not Neonatal CD4+CD3- Inducer Cells: Evidence That IL-7 Signals Regulate CD30 Ligand but Not OX40 Ligand Expression J. Immunol., June 1, 2005; 174(11): 6686 - 6691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. C. Gaspal, M.-Y. Kim, F. M. McConnell, C. Raykundalia, V. Bekiaris, and P. J. L. Lane Mice Deficient in OX40 and CD30 Signals Lack Memory Antibody Responses because of Deficient CD4 T Cell Memory J. Immunol., April 1, 2005; 174(7): 3891 - 3896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-P. Xia and Z. J. Chen TRAF2: A Double-Edged Sword? Sci. Signal., February 22, 2005; 2005(272): pe7 - pe7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mukundan, G. A. Bishop, K. Z. Head, L. Zhang, L. M. Wahl, and J. Suttles TNF Receptor-Associated Factor 6 Is an Essential Mediator of CD40-Activated Proinflammatory Pathways in Monocytes and Macrophages J. Immunol., January 15, 2005; 174(2): 1081 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhong and J. M. Kyriakis Germinal Center Kinase Is Required for Optimal Jun N-Terminal Kinase Activation by Toll-Like Receptor Agonists and Is Regulated by the Ubiquitin Proteasome System and Agonist-Induced, TRAF6-Dependent Stabilization Mol. Cell. Biol., October 15, 2004; 24(20): 9165 - 9175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Hayden and S. Ghosh Signaling to NF-{kappa}B Genes & Dev., September 15, 2004; 18(18): 2195 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivas-Carvalho, M. A. Meraz-Rios, L. Santos-Argumedo, S. Bajana, G. Soldevila, M. E. Moreno-Garcia, and C. Sanchez-Torres CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines Int. Immunol., September 1, 2004; 16(9): 1251 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Murray and I. N. Crispe TNF-{alpha} Controls Intrahepatic T Cell Apoptosis and Peripheral T Cell Numbers J. Immunol., August 15, 2004; 173(4): 2402 - 2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. McKee, F. Dzierszinski, M. Boes, D. S. Roos, and E. J. Pearce Functional Inactivation of Immature Dendritic Cells by the Intracellular Parasite Toxoplasma gondii J. Immunol., August 15, 2004; 173(4): 2632 - 2640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Weinberg, D. E. Evans, C. Thalhofer, T. Shi, and R. A. Prell The generation of T cell memory: a review describing the molecular and cellular events following OX40 (CD134) engagement J. Leukoc. Biol., June 1, 2004; 75(6): 962 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gil, M. A. Garcia, P. Gomez-Puertas, S. Guerra, J. Rullas, H. Nakano, J. Alcami, and M. Esteban TRAF Family Proteins Link PKR with NF-{kappa}B Activation Mol. Cell. Biol., May 15, 2004; 24(10): 4502 - 4512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-G. Xu, L.-Y. Li, and H.-B. Shu TRAF7 Potentiates MEKK3-induced AP1 and CHOP Activation and Induces Apoptosis J. Biol. Chem., April 23, 2004; 279(17): 17278 - 17282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Gentry, N. J. Rutkoski, T. L. Burke, and B. D. Carter A Functional Interaction between the p75 Neurotrophin Receptor Interacting Factors, TRAF6 and NRIF J. Biol. Chem., April 16, 2004; 279(16): 16646 - 16656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. So, S. Salek-Ardakani, H. Nakano, C. F. Ware, and M. Croft TNF Receptor-Associated Factor 5 Limits the Induction of Th2 Immune Responses J. Immunol., April 1, 2004; 172(7): 4292 - 4297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Park, D. Svetkauskaite, Q. He, J.-Y. Kim, D. Strassheim, A. Ishizaka, and E. Abraham Involvement of Toll-like Receptors 2 and 4 in Cellular Activation by High Mobility Group Box 1 Protein J. Biol. Chem., February 27, 2004; 279(9): 7370 - 7377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Matsuyama, L. Wang, W. L. Farrar, M. Faure, and T. Yoshimura Activation of Discoidin Domain Receptor 1 Isoform b with Collagen Up-Regulates Chemokine Production in Human Macrophages: Role of p38 Mitogen-Activated Protein Kinase and NF-{kappa}B J. Immunol., February 15, 2004; 172(4): 2332 - 2340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guillot, S. Medjane, K. Le-Barillec, V. Balloy, C. Danel, M. Chignard, and M. Si-Tahar Response of Human Pulmonary Epithelial Cells to Lipopolysaccharide Involves Toll-like Receptor 4 (TLR4)-dependent Signaling Pathways: EVIDENCE FOR AN INTRACELLULAR COMPARTMENTALIZATION OF TLR4 J. Biol. Chem., January 23, 2004; 279(4): 2712 - 2718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wan, L. Sun, J. W. Mendoza, Y. L. Chui, D. P. Huang, Z. J. Chen, N. Suzuki, S. Suzuki, W.-C. Yeh, S. Akira, et al. Elucidation of the c-Jun N-Terminal Kinase Pathway Mediated by Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Mol. Cell. Biol., January 1, 2004; 24(1): 192 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Li, P. S. Norris, C.-Z. Ni, M. L. Havert, E. M. Chiong, B. R. Tran, E. Cabezas, J. C. Reed, A. C. Satterthwait, C. F. Ware, et al. Structurally Distinct Recognition Motifs in Lymphotoxin-{beta} Receptor and CD40 for Tumor Necrosis Factor Receptor-associated Factor (TRAF)-mediated Signaling J. Biol. Chem., December 12, 2003; 278(50): 50523 - 50529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Frleta, R. J. Noelle, and W. F. Wade CD40-mediated up-regulation of Toll-like receptor 4-MD2 complex on the surface of murine dendritic cells J. Leukoc. Biol., December 1, 2003; 74(6): 1064 - 1073. [Abstract] [Full Text]
|
|
|
|
|
|
K. J. Savage, S. Monti, J. L. Kutok, G. Cattoretti, D. Neuberg, L. de Leval, P. Kurtin, P. D. Cin, C. Ladd, F. Feuerhake, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma Blood, December 1, 2003; 102(12): 3871 - 3879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akira Toll-like Receptor Signaling J. Biol. Chem., October 3, 2003; 278(40): 38105 - 38108. [Full Text] [PDF]
|
|
|
|
|
|
W. Matsuyama, M. Faure, and T. Yoshimura Activation of Discoidin Domain Receptor 1 Facilitates the Maturation of Human Monocyte-Derived Dendritic Cells Through the TNF Receptor Associated Factor 6/TGF-{beta}-Activated Protein Kinase 1 Binding Protein 1{beta}/p38{alpha} Mitogen-Activated Protein Kinase Signaling Cascade J. Immunol., October 1, 2003; 171(7): 3520 - 3532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Sax and W. S. El-Deiry Identification and Characterization of the Cytoplasmic Protein TRAF4 as a p53-regulated Proapoptotic Gene J. Biol. Chem., September 19, 2003; 278(38): 36435 - 36444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Polek, M. Talpaz, B. G. Darnay, and T. Spivak-Kroizman TWEAK Mediates Signal Transduction and Differentiation of RAW264.7 Cells in the Absence of Fn14/TweakR: EVIDENCE FOR A SECOND TWEAK RECEPTOR J. Biol. Chem., August 22, 2003; 278(34): 32317 - 32323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Henkler, B. Baumann, M. Fotin-Mleczek, M. Weingartner, R. Schwenzer, N. Peters, A. Graness, T. Wirth, P. Scheurich, J. A. Schmid, et al. Caspase-mediated Cleavage Converts the Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-1 from a Selective Modulator of TNF Receptor Signaling to a General Inhibitor of NF-{kappa}B Activation J. Biol. Chem., August 1, 2003; 278(31): 29216 - 29230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Reed, K. Doctor, A. Rojas, J. M. Zapata, C. Stehlik, L. Fiorentino, J. Damiano, W. Roth, S.-i. Matsuzawa, R. Newman, et al. Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans Genome Res., June 1, 2003; 13(6): 1376 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Donohue, C. M. Richards, S. A.N. Brown, H. N. Hanscom, J. Buschman, S. Thangada, T. Hla, M. S. Williams, and J. A. Winkles TWEAK Is an Endothelial Cell Growth and Chemotactic Factor That Also Potentiates FGF-2 and VEGF-A Mitogenic Activity Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 594 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Norman, W. Jiang, X. Han, T. L. Saunders, and J. S. Bond Targeted Disruption of the Meprin {beta} Gene in Mice Leads to Underrepresentation of Knockout Mice and Changes in Renal Gene Expression Profiles Mol. Cell. Biol., February 15, 2003; 23(4): 1221 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Eliopoulos, E. R. Waites, S. M. S. Blake, C. Davies, P. Murray, and L. S. Young TRAF1 Is a Critical Regulator of JNK Signaling by the TRAF-Binding Domain of the Epstein-Barr Virus-Encoded Latent Infection Membrane Protein 1 but Not CD40 J. Virol., December 20, 2002; 77(2): 1316 - 1328. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
