Journal article

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

James E Vince, Delara Pantaki, Rebecca Feltham, Peter D Mace, Stephanie M Cordier, Anna C Schmukle, Angelina J Davidson, Bernard A Callus, Wendy Wei-Lynn Wong, Ian E Gentle, Holly Carter, Erinna F Lee, Henning Walczak, Catherine L Day, David L Vaux, John Silke

J. Biol. Chem. | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2009

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 stim..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

Supported by a Human Frontiers science program fellowship.Recipient of a health sciences career development award (University of Otago).Supported by The Cancer Council Victoria.Australian Fellow, funded by the Leukemia and Lymphoma Society and National Health and Medical Research Council Grant 461221.Supported by National Health and Medical Research Council Grants 433013, 541901, and 541902.