The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Cell Death Differ. 2018 Jan;25(1):13-20. doi: 10.1038/cdd.2017.145. Epub 2017 Nov 3.
The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1. In that way, a cell suicide process that initially evolved as a mechanism for defense against intracellular parasites was then also used in multicellular organisms for morphogenesis and to maintain the correct number of cells in adults by balancing cell production by mitosis.
对 BCL2 的近 30 年研究将细胞死亡研究带入了分子时代，并揭示了其与人类病理生理学的相关性。如果不是所有后生动物，那么大多数后生动物都会使用一种进化上保守的细胞自我毁灭过程，该过程由与 BCL2 相关的蛋白质控制和执行。我们提出，抗凋亡的 BCL2 样蛋白和促凋亡的 BH3 仅成员是通过对多 BH 结构域家族成员（如 BAX 和 BAK1）的促凋亡基因的复制和修饰而产生的。这样，最初作为抵御细胞内寄生虫的防御机制而进化的细胞自杀过程，随后也被多细胞生物用于形态发生，并通过有丝分裂来平衡细胞的产生，从而维持成体中正确的细胞数量。
