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PMID: 8943045 Published · ppublish English Journal Article

The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 24 ·1996-11-26 ·Pages 13973-8

Shu HB, Takeuchi M, Goeddel DV

Abstract

The two cell surface receptors for tumor necrosis factor (TNF) interact with a number of intracellular signal transducing proteins. The association of TRADD, a 34-kDa cytoplasmic protein containing a C-terminal death domain, with aggregated TNF receptor 1 (TNF-R1) through their respective death domains leads to NF-kappa B activation and programmed cell death. In contrast, TNF receptor 2 (TNF-R2) interacts with the TNF receptor associated factors 2/1 (TRAF2/TRAF1) heterocomplex, which mediates the recruitment of two cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) to TNF-R2. Here we show that the TNF-R2 signal transducers TRAF2 and c-IAP1 are a part of the TNF-R1 signaling complex. The recruitment of TRAF2 and c-IAP1 to TNF-R1 is TNF-dependent, is mediated by TRADD, and is independent of TNF-R2. These data establish the physiological involvement of TRAF2 and c-IAP1 in TNF-R1 signaling and help provide a molecular explanation for both the overlapping and distinct signals generated by the two TNF receptors.

MeSH Terms
Antigens, CD/physiology Apoptosis Cell Line Cysteine Proteinase Inhibitors/physiology HeLa Cells Humans Inhibitor of Apoptosis Proteins Models, Biological NF-kappa B/metabolism Proteins/metabolism,physiology Receptors, Tumor Necrosis Factor/physiology Receptors, Tumor Necrosis Factor, Type I Receptors, Tumor Necrosis Factor, Type II Recombinant Proteins/metabolism,pharmacology Signal Transduction/physiology TNF Receptor-Associated Factor 1 TNF Receptor-Associated Factor 2 Transfection Tumor Necrosis Factor-alpha/pharmacology Ubiquitin-Protein Ligases
Chemicals
Antigens, CD Cysteine Proteinase Inhibitors Inhibitor of Apoptosis Proteins NF-kappa B Proteins Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Type I Receptors, Tumor Necrosis Factor, Type II Recombinant Proteins TNF Receptor-Associated Factor 1 TNF Receptor-Associated Factor 2 Tumor Necrosis Factor-alpha BIRC2 protein, human Ubiquitin-Protein Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shu H B
Tularik, Inc., South San Francisco, CA 94080, USA.
Takeuchi M
Goeddel D V
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36 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.24.13973
Published
1996-11-26
Pages
13973-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19479
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.24.13973 PMC Full Text View journal details
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