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.
TNF receptor crosstalk in apoptosis
TNF receptor crosstalk in apoptosis. J Cell Sci 1 July 2002; 115 (13): e1304. doi:
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