A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis.
A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis.
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DOI：
10.1007/978-1-4419-6612-4_62
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发表时间：
2011
影响因子：
--
通讯作者：
Chan, Francis Ka-Ming
中科院分区：
文献类型：
--
作者：
Cho, YoungSik;Challa, Sreerupa;Chan, Francis Ka-Ming
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 know 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.
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