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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-58109

Vince, J E; Pantaki, D; Feltham , R; Mace, P D; Cordier, S M; Schmukle, A C; Davidson, A J; Callus, B A; Wong, W. Wei-Lynn; Gentle, I E; Carter, H; Lee, E F; Walczak, H; Day, C L; Vaux, D L; Silke, J (2009). TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. Journal of Biological Chemistry, 284(51):35906-35915.

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Abstract

Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to cIAP1 and cIAP2 (cIAP1/2) and recruits them to the cytoplasmic domain of several members of the TNF receptor (TNFR) superfamily, including the TNF-TNFR1 ligand-receptor complex. Here, we define a cIAP1/2-interacting motif (CIM) within the TRAF-N domain of TRAF2, and we use TRAF2 CIM mutants to determine the role of TRAF2 and cIAP1/2 individually, and the TRAF2-cIAP1/2 interaction, in TNFR1-dependent signaling. We show that both the TRAF2 RING domain and the TRAF2 CIM are required to regulate NF-kappaB-inducing kinase stability and suppress constitutive noncanonical NF-kappaB activation. Conversely, following TNFR1 stimulation, cells bearing a CIM-mutated TRAF2 showed reduced canonical NF-kappaB activation and TNF-induced RIPK1 ubiquitylation. Remarkably, the RING domain of TRAF2 was dispensable for these functions. However, like the TRAF2 CIM, the RING domain of TRAF2 was required for protection against TNF-induced apoptosis. These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-kappaB signaling and that efficient activation of NF-kappaB by TNFR1 requires the recruitment of cIAP1/2 by TRAF2.

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76 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:15 Jun 2012 15:30
Last Modified:05 Jul 2014 14:02
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258 (P) 1083-351X (E)
Additional Information:This research was originally published in [Vince, J E; Pantaki, D; Feltham , R; Mace, P D; Cordier, S M; Schmukle, A C; Davidson, A J; Callus, B A; Wong, W. Wei-Lynn; Gentle, I E; Carter, H; Lee, E F; Walczak, H; Day, C L; Vaux, D L; Silke, J (2009). TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. Journal of Biological Chemistry, 284(51):35906-35915.]. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M109.072256
PubMed ID:19815541

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