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Sci. Signal., 20 March 2012
Vol. 5, Issue 216, p. ra22
[DOI: 10.1126/scisignal.2001878]


Editor's Summary

Directing TNFR Signaling with c-IAP
Binding of ligands to tumor necrosis factor receptors (TNFRs) recruits adaptor proteins and E3 ubiquitin ligases to form signaling complexes that activate NF-{kappa}B and MAPK signaling, which are important in development and immunity. Varfolomeev et al. defined the roles of the E3 ubiquitin ligases c-IAP1 and c-IAP2, which are recruited to the TNFR1 complex by the adaptor protein TRAF2. The c-IAPs were critical for NF-{kappa}B and MAPK activation and for recruiting distal signaling components to specific TNFRs, and loss of c-IAPs resulted in diminished signaling by these TNFRs. Conversely, TNFR family members that stimulated noncanonical NF-{kappa}B signaling, which is inhibited by a complex containing c-IAP proteins, caused the translocation of c-IAP proteins from the cytosol to the plasma membrane, resulting in their degradation. Together, these data suggest that c-IAP proteins regulate canonical and noncanonical NF-{kappa}B signaling as well as MAPK activation by TNFR family members.

Citation: E. Varfolomeev, T. Goncharov, H. Maecker, K. Zobel, L. G. Kömüves, K. Deshayes, D. Vucic, Cellular Inhibitors of Apoptosis Are Global Regulators of NF-{kappa}B and MAPK Activation by Members of the TNF Family of Receptors. Sci. Signal. 5, ra22 (2012).

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