RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis.
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-kappaB 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.
Ting
A T
AT
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114, USA.
Pimentel-Muiños
F X
FX
Seed
B
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter; D015151:Immunoblotting; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D016328:NF-kappa B / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D010768:Phosphoserine / Q000032:analysis / Q000378:metabolism; D010769:Phosphothreonine / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D019014:fas Receptor / Q000494:pharmacology*
D016328:NF-kappa B; D010718:Phosphatidylserines; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D010769:Phosphothreonine; D010768:Phosphoserine; D004247:DNA; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse