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

Adrian T. Ting, Felipe X. Pimentel-Muiños, Brian Seed

Research output: Contribution to journalArticlepeer-review

447 Scopus citations

Abstract

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-κB 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.

Original languageEnglish (US)
Pages (from-to)6189-6196
Number of pages8
JournalEMBO Journal
Volume15
Issue number22
DOIs
StatePublished - Nov 15 1996

Keywords

  • Apoptosis
  • Receptors
  • Signal transduction
  • Somatic cell mutant

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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