Abstract
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.
Highlights
THE BCL-2 PROTEIN FAMILY IN APOPTOSISApoptosis, the first described and probably best understood form of programed cell death, is a physiological process that actively leads to the death of a cell
Its regulation reaches the complexity of cell growth and cell proliferation, and a fine-tuned and self-regulatory balance between cell growth and cell death guarantees the healthy state of individual organisms (Singh et al, 2019)
Besides providing the current best evidence for a physiologically relevant role of BCL-2–related ovarian killer (BOK) in apoptosis and embryogenesis, this study demonstrated that multiple organs develop more or less normally in TKO mice and that a small proportion (1%) of TKO mice even survives into adulthood, indicating that intrinsic apoptosis is not strictly required for the development of mice (Ke et al, 2018)
Summary
The first described and probably best understood form of programed cell death, is a physiological process that actively leads to the death of a cell. Members of the BCL-2 family are central regulators of the so-called intrinsic, or mitochondrial, apoptotic pathway, a pathway that can be activated in possibly all cell types in response to a plethora of intrinsic stress (“apoptotic”) stimuli These include DNA damaging insults, oxidative stress, aberrant calcium fluxes, endoplasmic reticulum (ER) stress, nutrient deprivation, or infection by pathogens, among others (Lopez and Tait, 2015). Whereas regulation of the intrinsic apoptotic pathway, MOMP, is the best understood role of BCL-2 family members, it is important to mention that for most— if not all—members, other, distinct non-apoptotic roles have been described These range from modulating mitochondrial shape and metabolism, calcium flux, the unfolded protein response (UPR), DNA damage response, glucose and lipid metabolism to cellular proliferation and autophagy [reviewed in (Gross and Katz, 2017)]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
