BCL-2 family apoptosis regulator BOK (BOK)

BCL-2 family apoptosis regulator BOK (commonly known as BOK or BCL2-related ovarian killer) is a **pro-apoptotic member of the BCL-2 protein family** that regulates programmed cell death (apoptosis), predominantly in response to **endoplasmic reticulum (ER) stress**[5][7]. Like BAX and BAK, BOK contains several BH domains and a C-terminal transmembrane domain (TMD) that anchors it to intracellular membranes (mainly ER, also mitochondria and Golgi)[2][7]. Unlike BAX and BAK, most BOK is localized to the ER, and it is less prone to mitochondrial targeting. BOK can induce apoptosis when overexpressed and is regulated by interaction with anti-apoptotic BCL-2 proteins, often via TMD–TMD interactions, rather than the canonical BH3–hydrophobic groove interface[1][7]. Structural studies reveal BOK bears the BCL-2 family fold but has an **atypical, less accessible hydrophobic groove**, likely accounting for its unique regulatory and activation properties[6][7]. **BOK is closely involved in the apoptotic response to ER stress**, and unlike other BCL-2 family members, its loss specifically impairs this pathway rather than general apoptotic responses[5]. While drugs target the BCL-2 family in cancer therapy, **no drugs currently directly modulate BOK**, and its direct druggability remains under investigation[1][7]. BOK expression is regulated by cell cycle factors and stress signaling (e.g., E2F1, HIFs). Its roles beyond apoptosis may include influencing mitochondrial dynamics and calcium handling, though these mechanisms are not yet fully elucidated[2][7]. BOK is considered a promising but currently **untargeted apoptotic effector protein**, relevant for cancer biology and possibly as a marker of ER stress-induced apoptosis.

Other names

BCL2-related ovarian killerBCL2L9BOK protein

Pro-apoptotic activity: BOK promotes apoptosis primarily by inducing mitochondrial outer membrane permeabilization (MOMP) in response to stress, especially ER stress[5][7]. Its activity is regulated by direct interaction with anti-apoptotic BCL-2 family members, often via transmembrane domain (TMD) interactions[1][7]. Does not strongly bind most BH3-mimetic drugs, as the canonical hydrophobic BH3-binding groove of BOK is atypical, collapsed, or occluded compared to other BCL-2 family members[7][6].