A RNA Interference Screen Identifies RIP3 as an Essential Inducer of TNF-Induced Programmed Necrosis

  • YoungSik Cho
  • Sreerupa Challa
  • Francis Ka-Ming Chan
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


Recent evidence indicates that TNF-like death cytokines can induce apoptotic and non-apoptotic forms of cell death. We have coined the term “programmed necrosis” to describe caspase-independent cell death induced by TNF-like cytokines. Besides an obligate requirement for the protein serine/threonine kinase RIP1 and the production of reactive oxygen species (ROS), relatively little is known about the molecular mechanisms that control TNF-induced programmed necrosis. In order to further illuminate the molecular pathway that governs programmed necrosis, we performed a targeted RNA interference (RNAi) screen. Our screen identified RIP3, a RIP1 family member, as a specific mediator for programmed necrosis, but not apoptosis. Biochemical analyses show that assembly of the pro-necrotic RIP1–RIP3 complex critically regulates induction of programmed necrosis. The physiological relevance of RIP3-dependent programmed necrosis is demonstrated by the failure of RIP3-deficient mice to control vaccinia virus infections.


RIP3 Complex Vaccinia Virus Infection Riboflavin Kinase Control Reactive Oxygen Species Control Reactive Oxygen Species Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by NIH grant AI065877. F.K.C. was a recipient of investigator awards from the Smith Family Foundation and the Cancer Research Institute.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • YoungSik Cho
    • 1
    • 2
    • 3
  • Sreerupa Challa
    • 1
  • Francis Ka-Ming Chan
    • 1
  1. 1.Department of PathologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Immunology and Virology ProgramUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Center for Metabolic Syndrome Therapeutics, Bio-Organic Science DivisionKorea Research Institute of Chemical TechnologyDaejeonKorea

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