Journal of Cell Science 116, e1503 (2003)
Copyright © 2003 The Company of Biologists Limited
Interferon goes nuclear
-Interferon (IFN) is generally thought to act by binding to
cell surface receptors coupled to JAK-family kinases; these then phosphorylate
STAT transcription factors, causing them to translocate to the nucleus. Things
might not be so simple though: IFN can be endocytosed, and there is
some evidence that intracellular IFN has biological effects and can
even enter the nucleus. To examine the intracellular roles of IFN,
Iqbal Ahmed and co-workers have generated mutants that lack a secretory signal
and/or a nuclear localization signal (NLS) they have identified in the protein
(see p. 3089). They
find that the nonsecreted form has biological activities similar to those of
wild-type (extracellular) IFN, including antiviral effects and
upregulation of MHC class I molecules - if the NLS mutation is absent,
however, nonsecreted IFN is inactive. The authors go on to demonstrate
that intracellular IFN translocates to the nucleus as part of a complex
containing its receptor (IFNGR1), STAT1
and an importin - again this
requires the IFN NLS. They then show that extracellular IFN
undergoes receptor-mediated endocytosis and has NLS-dependent signalling
activity, thus providing good evidence that nuclear translocation of wild-type
IFN has a physiological role.
Related articles in JCS:
- The role of IFN nuclear localization sequence in intracellular function
- C. M. Iqbal Ahmed, Marjorie A. Burkhart, Mustafa G. Mujtaba, Prem S. Subramaniam, and Howard M. Johnson
JCS 2003 116: 3089-3098.
[Abstract]
[Full Text]
