Immunity. 2000 Mar;12(3):301-11.

Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation.External

Zhang, S. Q., Kovalenko, A., Cantarella, G., Wallach, D.,
--- - Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
The adapter protein RIP plays a crucial role in NF-kappaB activation by TNF. Here we show that triggering of the p55 TNF receptor induces binding of RIP to NEMO (IKKgamma), a component of the I-kappa-B-kinase (IKK) "signalosome" complex, as well as recruitment of RIP to the receptor together with the three major signalosome components, NEMO, IKK1 and IKK2, and some kind of covalent modification of the recruited RIP molecules. It also induces binding of NEMO to the signaling inhibitor A20, and recruitment of A20 to the receptor. Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex.
PMID: 10755617External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD FADD Link RIP Yeast two-hybrid Human Full length Yeast Human 580-671 Yeast 10755617
DD RIP Link RIP Yeast two-hybrid Human 580-671 Yeast Human Full length Yeast 10755617
DD RIP Link TRADD Yeast two-hybrid Human 580-671 Yeast Human Full length Yeast 10755617
(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
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD RIP Link TNFR1 Co-immunoprecipitation HEK293 Human Not specified Not used 10755617
(Link: click this icon to show interactions only between the two corresponding DDs)