RIP mediates tumor necrosis factor receptor 1 activation of NF- Kappa B but not Fas/APO-1-initiated apoptosis

• Published in: The EMBO journal Vol. 15; no. 22; pp. 6189 - 6196
• Main Authors: Ting, A T, Pimentel-Muinos, F X, Seed, B
• Format: Journal Article
• Language: English
• Published: 15.11.1996
• ISSN: 0261-4189
• DOI: 10.1002/j.1460-2075.1996.tb01007.x

The CD95 (Fas/APO-1) and tumor necrosis factor (TNF) receptor pathways share many similarities, including a common reliance on proteins containing 'death domains' for elements of the membrane-proximal signal relay. We have created mutant cell lines that are unable to activate NF- Kappa B in response to TNF. One of the mutant lines lacks RIP, a 74 kDa Ser/Thr kinase originally identified by its ability to associate with Fas/APO-1 and induce cell death. Reconstitution of the line with RIP restores responsiveness to TNF. The RIP-deficient cell line is susceptible to apoptosis initiated by anti-CD95 antibodies. An analysis of cells reconstituted with mutant forms of RIP reveals similarities between the action of RIP and FADD/MORT-1, a Fas-associated death domain protein.