MOMP, cell suicide as a BCL-2 family business.

MOMP, cell suicide as a BCL-2 family business.
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DOI:
10.1038/cdd.2017.179
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发表时间:
2018-01
影响因子:
12.4
通讯作者:
Green DR
Green DR
中科院分区:
生物学1区
文献类型:
--
作者:
Kalkavan H;Green DR

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细胞凋亡塑造发育和分化,在组织稳态中起关键作用,并且在癌症中失调。在大多数情况下,成功的细胞凋亡是由线粒体外膜透化(MOMP)触发的,其定义了线粒体或内在途径,并最终导致半胱天冬酶活化和蛋白质底物裂解。以MOMP为中心的线粒体凋亡途径由一个复杂的事件网络控制,该事件网络决定了细胞命运在存活和死亡之间的平衡。在这里,我们将审查MOMP如何进行,以及如何主要效应细胞色素c,血红素蛋白,在呼吸中起着至关重要的作用,和第二个胱天蛋白酶(SMAC),以及其他膜间空间蛋白,编排胱天蛋白酶激活。此外,我们讨论了最近的见解的上游协调员和发起人的MOMP,BCL-2家族的相互作用。这篇综述强调了我们对细胞凋亡关键检查点调控的认识如何与对癌症发展的理解相结合,并已开始转化为治疗的临床益处。
Apoptosis shapes development and differentiation, has a key role in tissue homeostasis, and is deregulated in cancer. In most cases, successful apoptosis is triggered by mitochondrial outer membrane permeabilization (MOMP), which defines the mitochondrial or intrinsic pathway and ultimately leads to caspase activation and protein substrate cleavage. The mitochondrial apoptotic pathway centered on MOMP is controlled by an intricate network of events that determine the balance of the cell fate choice between survival and death. Here we will review how MOMP proceeds and how the main effectors cytochrome c, a heme protein that has a crucial role in respiration, and second mitochondria-derived activator of caspase (SMAC), as well as other intermembrane space proteins, orchestrate caspase activation. Moreover, we discuss recent insights on the interplay of the upstream coordinators and initiators of MOMP, the BCL-2 family. This review highlights how our increasing knowledge on the regulation of critical checkpoints of apoptosis integrates with understanding of cancer development and has begun to translate into therapeutic clinical benefit.
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