Skip to Main content Skip to Navigation
Journal articles

Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.

Olivier Micheau 1 Jürg Tschopp 1, *
* Corresponding author
Abstract : Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
Document type :
Journal articles
Complete list of metadatas

Cited literature [37 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00527105
Contributor : Olivier Micheau <>
Submitted on : Monday, October 18, 2010 - 10:43:16 AM
Last modification on : Monday, October 18, 2010 - 2:42:23 PM
Long-term archiving on: : Wednesday, January 19, 2011 - 2:39:58 AM

Files

TNF-R1complexTschopp.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : inserm-00527105, version 1
  • PUBMED : 12887920

Collections

Citation

Olivier Micheau, Jürg Tschopp. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.. Cell, Elsevier, 2003, 114 (2), pp.181-90. ⟨inserm-00527105⟩

Share

Metrics

Record views

505

Files downloads

2132