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

EMBO J. 1996 Nov 15;15(22):6189-96.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Blotting, Western
  • Cells, Cultured
  • DNA / metabolism
  • Flow Cytometry
  • Gene Expression Regulation / genetics
  • Genes, Reporter
  • Immunoblotting
  • Mice
  • Mutagenesis / genetics
  • NF-kappa B / pharmacology*
  • Phosphatidylserines / metabolism
  • Phosphoserine / analysis
  • Phosphoserine / metabolism
  • Phosphothreonine / analysis
  • Phosphothreonine / metabolism
  • Proteins / pharmacology*
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor / agonists
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Transfection / genetics
  • fas Receptor / pharmacology*


  • NF-kappa B
  • Phosphatidylserines
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • fas Receptor
  • Phosphothreonine
  • Phosphoserine
  • DNA
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse