Site-specific Lys-63-linked Tumor Necrosis Factor Receptor-associated Factor 6 Auto-ubiquitination Is a Critical Determinant of IκB Kinase Activation

Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key mediator in proximal signaling of the interleukin-1/Toll-like receptor and the TNF receptor superfamily. Analysis of TRAF6-deficient mice revealed a fundamental role of TRAF6 in osteoclastogenesis; however, the molecular mechanism underlying TRAF6 signaling in this biological process is not understood. Recent biochemical evidence has indicated that TRAF6 possesses ubiquitin ligase activity that controls the activation of IKK and NF-κB. Because these studies are primarily based on cell-free systems, the role of the ubiquitin ligase activity of TRAF6 and its auto-ubiquitination the in that of TRAF6 in the is auto-ubiquitination of TRAF6 and its IKK and NF-κB. a of TRAF6 its receptor of and of the factor the auto-ubiquitination of TRAF6 a TRAF6 and IKK and biochemical and in evidence that TRAF6 TRAF6 the the TRAF6 and auto-ubiquitination of TRAF6 IKK in a signaling in TRAF6 auto-ubiquitination is the mediator of Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key mediator in proximal signaling of the interleukin-1/Toll-like receptor and the TNF receptor superfamily. Analysis of TRAF6-deficient mice revealed a fundamental role of TRAF6 in osteoclastogenesis; however, the molecular mechanism underlying TRAF6 signaling in this biological process is not understood. Recent biochemical evidence has indicated that TRAF6 possesses ubiquitin ligase activity that controls the activation of IKK and NF-κB. Because these studies are primarily based on cell-free systems, the role of the ubiquitin ligase activity of TRAF6 and its auto-ubiquitination the in that of TRAF6 in the is auto-ubiquitination of TRAF6 and its IKK and NF-κB. a of TRAF6 its receptor of and of the factor the auto-ubiquitination of TRAF6 a TRAF6 and IKK and biochemical and in evidence that TRAF6 TRAF6 the the TRAF6 and auto-ubiquitination of TRAF6 IKK in a signaling in TRAF6 auto-ubiquitination is the mediator of necrosis and and TNF receptor-associated receptor of factor of activation ubiquitin necrosis and and TNF receptor-associated receptor of factor of activation ubiquitin and necrosis factor (TNF) a in the receptor these a of signaling the activation of and and the and in the and of receptor-associated a of and of in activation of the factor and of the the of of the TNF receptor a the the of the is of and in a has in a of ubiquitin the of TRAF6 has in a of ubiquitin a of and a that TRAF6 possesses ligase activity 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