Chronicles of a death foretold: Dual sequential cell death checkpoints in TNF signaling

Marie Anne O'Donnell, Adrian T. Ting

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


The kinase RIP1 wears a coat of many colors during TNF receptor signaling and can regulate both activation of prosurvival NFκB and programmed cell death pathways. In this review, we outline how coating RIP1 with K63-linked ubiquitin chains forms a protective layer that prevents RIP1 from binding apoptotic regulators and serves as an early guard against cell death. Further on, binding of NFκB signaling components to the ubiquitin coat of RIP1 activates long-term pro-survival signaling and forms a more impenetrable suit of armor against cell death. If RIP1 is not decorated with ubiquitin chains it becomes an unstoppable harbinger of bad news: programmed cell death.

Original languageEnglish (US)
Pages (from-to)1065-1071
Number of pages7
JournalCell Cycle
Issue number6
StatePublished - Mar 15 2010


  • Apoptosis
  • IAP
  • NFκB
  • Necrosis
  • RIP
  • TNF
  • TRAF
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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