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仅含BH3结构域的蛋白质会引发细胞色素c的释放,但具体机制是怎样的呢?

BH3-only proteins trigger cytochrome c release, but how?

作者信息

Häcker Georg, Weber Arnim

机构信息

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.

出版信息

Arch Biochem Biophys. 2007 Jun 15;462(2):150-5. doi: 10.1016/j.abb.2006.12.022. Epub 2007 Jan 9.

Abstract

The mitochondrial apoptosis pathway has been neatly ordered. Mitochondrial apoptosis is governed by Bcl-2 family proteins, and their respective contributions determine the release of cytochrome c. It is clear that, among the Bcl-2 family, BH3-only proteins are the triggers: activation of BH3-only proteins by apoptotic stimuli initiates the process. BH3-only proteins cause cytochrome c release by activating Bax and/or Bak, and the anti-apoptotic group of Bcl-2-like proteins prevents this. However, it is curiously uncertain how BH3-only proteins activate Bax/Bak. Current models suggest that this is either through direct interaction--although this interaction is not detectable experimentally--or by the neutralisation of Bcl-2-like proteins. Here we discuss the context in which these models are placed and attempt to weigh the evidence.

摘要

线粒体凋亡途径已被清晰地梳理出来。线粒体凋亡受Bcl-2家族蛋白调控,它们各自的作用决定了细胞色素c的释放。很明显,在Bcl-2家族中,仅含BH3结构域的蛋白是触发因素:凋亡刺激激活仅含BH3结构域的蛋白从而启动这一过程。仅含BH3结构域的蛋白通过激活Bax和/或Bak导致细胞色素c释放,而Bcl-2样蛋白的抗凋亡基团则阻止这种情况发生。然而,奇怪的是,目前尚不清楚仅含BH3结构域的蛋白是如何激活Bax/Bak的。目前的模型表明,这要么是通过直接相互作用——尽管这种相互作用在实验中无法检测到——要么是通过中和Bcl-2样蛋白来实现。在此我们讨论这些模型所处的背景,并尝试权衡相关证据。

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