RNA 干扰筛选鉴定 RIP3 为 TNF 诱导的程序性细胞坏死的必需诱导剂。
A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis.
机构信息
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
出版信息
Adv Exp Med Biol. 2011;691:589-93. doi: 10.1007/978-1-4419-6612-4_62.
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.
最近的证据表明，TNF 样死亡细胞因子可诱导细胞发生凋亡和非凋亡形式的死亡。我们创造了“程序性细胞坏死”这一术语，用于描述 TNF 样细胞因子诱导的 caspase 非依赖性细胞死亡。除了需要蛋白丝氨酸/苏氨酸激酶 RIP1 和活性氧（ROS）的产生之外，关于控制 TNF 诱导的程序性细胞坏死的分子机制还知之甚少。为了进一步阐明调控程序性细胞坏死的分子途径，我们进行了靶向 RNA 干扰（RNAi）筛选。我们的筛选鉴定出 RIP3，一种 RIP1 家族成员，是程序性细胞坏死的特定介质，但不是凋亡。生化分析表明，促坏死的 RIP1-RIP3 复合物的组装对程序性细胞坏死的诱导具有关键调控作用。RIP3 依赖性程序性细胞坏死的生理相关性通过 RIP3 缺陷型小鼠无法控制牛痘病毒感染得到证明。
Zotero 插件