Naim Samara, Kaufmann Thomas
Institute of Pharmacology, University of Bern, Bern, Switzerland.
Front Cell Dev Biol. 2020 Sep 15;8:574338. doi: 10.3389/fcell.2020.574338. eCollection 2020.
BCL-2-related ovarian killer (BOK) is-despite its identification over 20 years ago-an incompletely understood member of the BCL-2 family. BCL-2 family proteins are best known for their critical role in the regulation of mitochondrial outer membrane permeabilization during the intrinsic apoptotic pathway. Based on sequence and structural similarities to BAX and BAK, BOK is grouped with these "killers" within the effector subgroup of the family. However, the mechanism of how exactly BOK exerts apoptosis is not clear and controversially discussed. Furthermore, and in accordance with reports on several other BCL-2 family members, BOK seems to be involved in the regulation of a variety of other, "apoptosis-independent" cellular functions, including the unfolded protein response, cellular proliferation, metabolism, and autophagy. Of note, compared with other proapoptotic BCL-2 family members, BOK levels are often reduced in cancer by various means, and there is increasing evidence for BOK modulating tumorigenesis. In this review, we summarize and discuss apoptotic- and non-apoptotic-related functions of BOK, its regulation as well as its physiological and pathophysiological roles.
BCL-2相关卵巢杀手蛋白（BOK）尽管在20多年前就已被发现，但它仍是BCL-2家族中一个尚未被完全了解的成员。BCL-2家族蛋白最为人所知的是它们在内在凋亡途径中线粒体外膜通透性调节方面的关键作用。基于与BAX和BAK的序列及结构相似性，BOK被归为该家族效应子亚组中的这些“杀手”蛋白。然而，BOK究竟如何发挥凋亡作用的机制尚不清楚，且存在争议。此外，与其他几个BCL-2家族成员的报道一致，BOK似乎参与调节多种其他“非凋亡依赖性”细胞功能，包括未折叠蛋白反应、细胞增殖、代谢和自噬。值得注意的是，与其他促凋亡BCL-2家族成员相比，BOK水平在癌症中常通过多种方式降低，并且越来越多的证据表明BOK可调节肿瘤发生。在本综述中，我们总结并讨论了BOK的凋亡及非凋亡相关功能、其调节以及生理和病理生理作用。
