Immunity
Volume 12, Issue 3, 1 March 2000, Pages 301-311
Journal home page for Immunity

Article
Recruitment of the IKK Signalosome to the p55 TNF Receptor: RIP and A20 Bind to NEMO (IKKγ) upon Receptor Stimulation

https://doi.org/10.1016/S1074-7613(00)80183-1Get rights and content
Under an Elsevier user license
open archive

Abstract

The adapter protein RIP plays a crucial role in NF-κB activation by TNF. Here we show that triggering of the p55 TNF receptor induces binding of RIP to NEMO (IKKγ), a component of the I-κ-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-κB 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.

Cited by (0)