Journal of Cell Science 115, e1304-e1304 (2002)
© 2002 The Company of Biologists Limited
TNF receptor crosstalk in apoptosis
Tumor necrosis factor (TNF) binds to two cell surface receptors: TNF-R1 and
TNF-R2. TNF-R1 possesses a death domain (DD) required for TNF-induced
apoptosis. The DD recruits the adaptor protein TRADD, which binds to a second
adaptor (FADD) that in turns recruit caspase-8 — the enzyme that
initiates the apoptotic programme. In contrast to TNF-R1, TNF-R2 lacks a DD.
It appears to enhance apoptotic signalling by TNF-R1, but how it does so is
unclear. Studies by Harald Wajant and co-workers now shed light on the role of
this receptor (see p. 2757).
The authors find that stimulation of TNF-R2 causes it to bind TRAF-2 —
an adaptor that can recruit anti-apoptotic proteins cIAP1 and cIAP2 to
TNFR1-bound TRADD — and deplete it from the cytosol. Using live-cell
imaging and confocal microscopy, they demonstrate that TNF-R2 competes with
TNF-R1 for the cIAPs and accelerates activation of caspase-8 by TNF-R1. TNF-R2
thus acts as a decoy for the anti-apoptotic factors, allowing TNF-R1-bound
TRADD to concentrate on recruiting proapoptotic FADD and caspase-8.
Related articles in JCS:
- Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8
- Mariola Fotin-Mleczek, Frank Henkler, Dierk Samel, Monica Reichwein, Angelika Hausser, Ingela Parmryd, Peter Scheurich, Johannes A. Schmid, and Harald Wajant
JCS 2002 115: 2757-2770.
[Abstract]
[Full Text]
