BCL-2 family proteins: changing partners in the dance towards death.
BCL-2 family proteins: changing partners in the dance towards death.
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DOI：
10.1038/cdd.2017.186
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发表时间：
2018-01
影响因子：
12.4
通讯作者：
Andrews DW
中科院分区：
文献类型：
--
作者：
Kale J;Osterlund EJ;Andrews DW
BCL-2蛋白家族主要通过直接结合相互作用控制细胞死亡，这种相互作用调节线粒体外膜通透性（MOMP），导致膜间空间蛋白的不可逆释放，随后的半胱天冬酶激活和细胞凋亡。BCL-2家族蛋白的亲和力和相对丰度决定了调控MOMP的抗凋亡和促凋亡BCL-2家族蛋白之间的主要相互作用。我们强调了BCL-2家族调控MOMP的核心机制，重点是BCL-2家族蛋白之间的相互作用如何控制细胞命运。我们讨论了BCL-2家族蛋白的浓度和亲和力的关键重要性，并展示了两者的差异如何极大地改变结果。此外，我们解释了使用全长BCL-2家族蛋白（相对于截断的版本或肽）来解析BCL-2家族调控MOMP的核心机制的重要性。最后，我们讨论了翻译后修饰和不同的细胞内定位如何改变BCL-2家族蛋白调控细胞凋亡的机制。人类疾病中MOMP调节的成功治疗干预需要了解介导细胞中BCL-2家族蛋白之间主要结合相互作用的因素。
The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis. The affinities and relative abundance of the BCL-2 family proteins dictate the predominate interactions between anti-apoptotic and pro-apoptotic BCL-2 family proteins that regulate MOMP. We highlight the core mechanisms of BCL-2 family regulation of MOMP with an emphasis on how the interactions between the BCL-2 family proteins govern cell fate. We address the critical importance of both the concentration and affinities of BCL-2 family proteins and show how differences in either can greatly change the outcome. Further, we explain the importance of using full-length BCL-2 family proteins (versus truncated versions or peptides) to parse out the core mechanisms of MOMP regulation by the BCL-2 family. Finally, we discuss how post-translational modifications and differing intracellular localizations alter the mechanisms of apoptosis regulation by BCL-2 family proteins. Successful therapeutic intervention of MOMP regulation in human disease requires an understanding of the factors that mediate the major binding interactions between BCL-2 family proteins in cells.