PMID:15861135
| Citation |
Wu, CJ, Conze, DB, Li, X, Ying, SX, Hanover, JA and Ashwell, JD (2005) TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. EMBO J. 24:1886-98 |
|---|---|
| Abstract |
Signaling through tumor necrosis factor receptor 2 (TNF-R2) results in ubiquitination of TRAF2 by the E3 c-IAP1. In this report, we confirm that TRAF2 translocates to a Triton X-100 (TX)-insoluble compartment upon TNF-R2 engagement. Moreover, TRAF2 ubiquitination occurs in this compartment, from which TRAF2 is degraded in a proteasome-dependent manner. Confocal microscopy demonstrated that the TX-insoluble compartment is perinuclear and co-localizes with endoplasmic reticulum (ER) markers. The ER transmembrane Ubc6 bound to c-IAP1 and served as a cognate E2 for c-IAP1's E3 activity in vitro. Furthermore, Ubc6 co-localized with translocated TRAF2/c-IAP1 in the ER-associated compartment in vivo, and a catalytically inactive Ubc6 mutant inhibited TNF-alpha-induced, TNF-R2-dependent TRAF2 degradation. These results indicate that upon TNF-R2 signaling, translocation of TRAF2 and c-IAP1 to an ER-associated, Ubc6-containing perinuclear compartment is required for the ubiquitination of TRAF2 by c-IAP1. Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. |
| Links |
PubMed PMC1142588 Online version:10.1038/sj.emboj.7600649 |
| Keywords |
Animals; COS Cells; Cell Nucleus/metabolism; Cercopithecus aethiops; Endoplasmic Reticulum/metabolism; Humans; Inhibitor of Apoptosis Proteins; Jurkat Cells; Proteins/metabolism; Receptors, Tumor Necrosis Factor, Type II/metabolism; TNF Receptor-Associated Factor 2/metabolism; Tumor Necrosis Factor-alpha/metabolism; Ubiquitin/metabolism; Ubiquitin-Conjugating Enzymes/metabolism |
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