Immunity. 2000 Apr;12(4):419-29.

The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation.External

Devin, A., Cook, A., Lin, Y., Rodriguez, Y., Kelliher, M., Liu, Z.,
--- - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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-kappaB, 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.
PMID: 10795740External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD RIP Link TNFR1 Co-immunoprecipitation Fibroblast 10795740
DD TNFR1 Link TRADD Co-immunoprecipitation Fibroblast 10795740
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DD RIP Link TNFR1 IKK assay NF-kB activation (DISC) 10795740
DD TNFR1 Link TRADD IKK assay NF-kB activation (DISC) 10795740
(Link: click this icon to show interactions only between the two corresponding DDs)