New perspectives in TNF-R1-Induced NF-κB signaling

Abstract

The ubiquitylation events leading to activation of NF-κB at the TNFR1 receptor have been a topic of intense study. It is believed that K63 ubiquitylation of the kinase RIPK1 is required for recruitment of the TAB2/TAB3/TAK1 and IKK1/IKK2/NEMO complexes that are in turn required to phosphorylate and degrade IκBα allowing freed NF-κB dimers to nuclear translocation. The exact involvement of the E3 ligases, TRAF2, TRAF5, cIAP1, and cIAP2 in this process has been unclear. We summarize a recent study from our lab defining the roles of TRAF2 and cIAP1 s in activation of NF-κB downstream of TNF-R1 and report the surprising finding that RIPK1 is not essential for TNF-R1-induced NF-κB. Alternative mechanisms of how NF-κB may be activated by TNF-R1 in the light of these findings are discussed. © 2011 Springer Science+Business Media, LLC.