Bax activation and mitochondrial insertion during apoptosis
Bax activation and mitochondrial insertion during apoptosis
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DOI：
10.1007/s10495-007-0749-1
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发表时间：
2007-05-01
期刊：
影响因子：
7.2
通讯作者：
Vallette, Francois M.
中科院分区：
文献类型：
--
作者：
Lalier, Lisenn;Cartron, Pierre-Francois;Vallette, Francois M.
线粒体凋亡途径是决定细胞命运的高度调节的生物学机制。它被定义为一系列事件，从细胞凋亡刺激到细胞膜透化，导致所谓的执行阶段的激活。在癌细胞中，这一途径经常发生改变，线粒体的通透性变化受Bcl-2蛋白家族（pBcls）的控制。这些蛋白质与Bcl-2共享一至四个同源结构域（设计为BH 1 -4），并且易于同源和/或异源二聚化。尽管氨基酸序列同源性差，但这些蛋白质表现出非常相似的三级结构。引人注目的是，虽然这些蛋白质中的一些是抗凋亡的，但其他蛋白质是促凋亡的。促凋亡蛋白进一步分为两个亚类：多结构域蛋白，其中Bax和巴克，其表现出BH 1 -3结构域，和仅BH 3蛋白（或BOP）。示意性地，BOP和抗凋亡蛋白拮抗性地调节多结构域蛋白Bax和巴克的激活和它们的寡聚化，后者的过程是负责凋亡的线粒体permeabilization.Considering的Bax在癌细胞凋亡中的关键作用，我们集中在这篇综述中的Bax激活的分子事件，通过其与Bcl-2家族的其他蛋白质的相互作用。Bax一旦被激活，触发细胞膜透化的机制将在本期特刊的其他综述中讨论。
The mitochondrial apoptotic pathway is a highly regulated biological mechanism which determines cell fate. It is defined as a cascade of events, going from an apoptotic stimulus to the MOM permeabilization, resulting in the activation of the so-called executive phase. This pathway is very often altered in cancer cells.The mitochondrial permeabilization is under the control of the Bcl-2 family of proteins (pBcls). These proteins share one to four homology domains (designed BH1-4) with Bcl-2, and are susceptible of homo- and/or hetero-dimerization. In spite of a poor amino-acid sequence homology, these proteins exhibit very similar tertiary structures. Strikingly, while some of these proteins are anti-apoptotic, the others are pro-apoptotic. Pro-apoptotic proteins are further divided in two sub-classes: multi-domains proteins, among which Bax and Bak, which exhibit BH1-3 domains, and BH3-only proteins (or BOPs). Schematically, BOPs and anti-apoptotic proteins antagonistically regulate the activation of the multi-domain proteins Bax and Bak and their oligomerization in the MOM, the latter process being responsible for the apoptotic mitochondrial permeabilization.Considering the critical role of Bax in cancer cells apoptosis, we focus in this review on the molecular events of Bax activation through its interaction with the other proteins from the Bcl-2 family. The mechanism by which Bax triggers the MOM permeabilization once activated will be discussed in some other reviews in this special issue.