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:
Download citation file:
Advertisement
Cited by
Introducing our new Editors
We welcome three new Editors to Journal of Cell Science - Robert Parton, Richa Rikhy and Simon Cook. You can read more about them in the Editorial from our Editor-in-Chief Michael Way.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Final registration deadline: 3 May 2024.
Workshop: Physics of the Early Embryonic Cell Divisions
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 11-14 November 2024. Application deadline: 17 May.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.
Propose a new Workshop for 2026
We are now accepting proposals for our 2026 Workshops programme. We aim to be responsive to the community and open to novel initiatives, so if you have a new idea for a biological workshop that you feel would work well, please apply. Applications deadline: 19 July 2024.