Youle Richard J, Strasser Andreas
Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59. doi: 10.1038/nrm2308.
BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host-pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
BCL-2家族蛋白具有促凋亡或抗凋亡活性，在过去十年中一直受到深入研究，因为它们在细胞凋亡调控、肿瘤发生以及细胞对抗癌治疗的反应中具有重要作用。它们控制着克隆形成细胞存活的不可逆转点，从而影响肿瘤发生和宿主-病原体相互作用，并调节动物发育。然而，最近的结构、系统发育和生物学分析表明，需要对该家族公认的组织原则以及家族成员在程序性细胞死亡过程中如何相互作用进行一些重新思考。尽管这些对BCL-2家族蛋白相互作用的见解揭示了这些蛋白是如何被调控的，但关于它们激活半胱天冬酶所使用机制的统一假说仍然难以捉摸。
