Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Complexes

Cell. 114, 181-190.

Speaker: 張綱凡

Commentator: 劉校生 教授

Time: 92/10/01 14:00~15:00

Place: Room 601

Abstract:

      The tumor necrosis factor receptor 1 (TNFR1), a prototypic member of the death receptor family, signals both cell survival and apoptosis. Despite the extensive study of this receptor, the mechanism governing the decision to induce one of these pathways over the other is very poorly understood.  After the identification of the components of the death inducing signaling complex (DISC) of the related death receptor CD95 (Fas), it was widely assumed that TNFR1 would also initiate apoptosis in the similar manner. The authors demonstrated in this study that, unlike the Fas signaling pathway, the TNFR1-induced proapoptotic signaling pathway requires the formation of two sequential and distinct signaling complexes. The rapidly formed plasma membrane bound complex I  (consists of TNFR1, TRADD, RIP, TRAF2, and c-IAP1) and triggers the activation of NF-κB. A second complex, which lacks TNFR1 but includes FADD and procaspase-8 and -10, subsequently forms in the cytoplasm and commits to cell death. The authors also found that the first complex I can not only activate survival signals but also influence the activity of the second complex. Thus, the authors suggest that this mechanism provide a checkpoint to control the TNFR1-mediated cell apoptosis.

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3. Micheau,O., et al. Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes. Cell. 114, 181-190 (2003).

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