[PDF][PDF] The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation

A Devin, A Cook, Y Lin, Y Rodriguez, M Kelliher, Z Liu - Immunity, 2000 - cell.com
A Devin, A Cook, Y Lin, Y Rodriguez, M Kelliher, Z Liu
Immunity, 2000cell.com
The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are
essential effectors in TNF signaling. To understand the mechanism by which RIP and TRAF2
regulate TNF-induced activation of the transcription factor NF-κB, we investigated their
respective roles in TNF-R1-mediated IKK activation using both RIP−/− and TRAF2−/−
fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2
proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex …
Abstract
The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are essential effectors in TNF signaling. To understand the mechanism by which RIP and TRAF2 regulate TNF-induced activation of the transcription factor NF-κB, we investigated their respective roles in TNF-R1-mediated IKK activation using both RIP−/− and TRAF2−/− fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation. Moreover, we demonstrated that IKK is recruited to the TNF-R1 complex through TRAF2 upon TNF treatment and that IKK activation requires the presence of RIP in the same complex.
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