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

The adapter protein RIP plays a crucial role in NF-KB activation by TNF. He re we show that triggering of the p55 TNF receptor induces binding of RIP t o NEMO (IKK gamma), a component of the I-kappa-B-kinase (IKK) "signalosome" complex, as well as recruitment of RIP to the receptor together with the t hree major signalosome components, NEMO, IKK1 and 1KK2, and some kind of co valent modification of the recruited RIP molecules. It also induces binding of NEMO to the signaling inhibitor A20, and recruitment of A20 to the rece ptor. Enforced expression of NEMO in cells revealed that NEMO can both prom ote and block NF-kappa B activation and dramatically augments the phosphory lation 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.