Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
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DOI：
10.1016/j.tips.2016.12.005
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发表时间：
2017-03
影响因子：
13.8
通讯作者：
Degterev A
中科院分区：
文献类型：
--
作者：
Wegner KW;Saleh D;Degterev A
被称为坏死性凋亡的调节性坏死过程已被认为是在广泛的病理环境下发生的细胞死亡和炎症的主要贡献者。坏死性凋亡中的核心事件是同源Ser/Thr激酶受体相互作用激酶1（RIPK 1）和受体相互作用激酶3（RIPK 3）的洗涤剂不溶性“坏死体”复合物的形成，其通过RIPK 3促进关键促死亡效应物混合谱系激酶结构域样（MLKL）的磷酸化。核心坏死性凋亡介质处于多种控制之下，这一直是深入研究的主题。此外，这些因子的非坏死性功能，主要是控制细胞凋亡和炎症反应，也开始出现。这篇综述将提供一个概述，目前的理解人类疾病的相关性，这一途径，和潜在的治疗策略，针对坏死性凋亡介质在各种病理。
A process of regulated necrosis, termed necroptosis, has been recognized as a major contributor to cell death and inflammation occurring under a wide range of pathologic settings. The core event in necroptosis is the formation of the detergent-insoluble “necrosome” complex of homologous Ser/Thr kinases Receptor Interacting Kinase 1 (RIPK1) and Receptor Interacting Kinase 3 (RIPK3), which promotes phosphorylation of a key pro-death effector Mixed Lineage Kinase Domain-like (MLKL) by RIPK3. Core necroptosis mediators are under multiple controls, which have been a subject of intense investigation. Additional, non-necroptotic functions of these factors, primarily in controlling apoptosis and inflammatory responses, have also begun to emerge. This review will provide an overview of the current understanding of the human disease relevance of this pathway, and potential therapeutic strategies, targeting necroptosis mediators in various pathologies.