半胱天冬酶 -8 的增殖与凋亡功能：异源或同源二聚体：半胱天冬酶 -8 二聚体控制细胞命运。
Proliferative versus apoptotic functions of caspase-8 Hetero or homo: the caspase-8 dimer controls cell fate.
作者信息
van Raam Bram J, Salvesen Guy S
机构信息
Program of Apoptosis and Cell Death Research, Sanford-Burnham Institute, La Jolla, CA 92037, USA.
出版信息
Biochim Biophys Acta. 2012 Jan;1824(1):113-22. doi: 10.1016/j.bbapap.2011.06.005. Epub 2011 Jun 16.
Abstract
Caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. It has become increasingly clear that the heterodimer of caspase-8 with the long isoform of cellular FLIP (FLIP(L)) fulfills these pro-survival functions of caspase-8. FLIP(L), a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIP(L) heterodimer has a restricted substrate repertoire and does not induce apoptosis. In essence, caspase-8 heterodimerized with FLIP(L) prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis. This review discusses the latest insights in caspase-8 homo- versus heterodimerization and the implication this has for cellular death or survival. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
摘要
半胱天冬酶 -8 是外源性触发凋亡的起始因子，在多种细胞表面受体下游的细胞活化和分化过程中也发挥着重要作用。越来越清楚的是，半胱天冬酶 -8 与细胞型 FLIP 的长异构体（FLIP(L)）形成的异二聚体实现了半胱天冬酶 -8 的这些促生存功能。FLIP(L) 是一种催化缺陷型半胱天冬酶 -8 旁系同源物，可与半胱天冬酶 -8 相互作用以激活其催化功能。半胱天冬酶 -8/FLIP(L) 异二聚体具有有限的底物谱，不会诱导细胞凋亡。本质上，与 FLIP(L) 异二聚化的半胱天冬酶 -8 可防止受体相互作用激酶 RIPK1 和 -3 执行称为坏死性凋亡的细胞死亡形式。本综述讨论了半胱天冬酶 -8 同二聚化与异二聚化的最新见解及其对细胞死亡或存活的影响。本文是名为：溶酶体发现 50 年后的蛋白水解的特刊的一部分。
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