The Multifaceted Roles of the BCLL-2 Family Member BOK

Naim, Samara; Kaufmann, Thomas (2020). The Multifaceted Roles of the BCLL-2 Family Member BOK. Frontiers in cell and developmental biology, 8 Frontiers 10.3389/fcell.2020.574338

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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.

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