Bcl-2-related ovarian killer (BOK)

Bcl-2-related ovarian killer (BOK) is a pro-apoptotic member of the BCL-2 protein family, structurally categorized as a multi-domain protein similar to BAX and BAK (UniProt: O00584). Unlike its more famous relatives, BOK is primarily localized to the endoplasmic reticulum (ER) and Golgi apparatus and is characterized by its extreme instability, being constitutively targeted for degradation by the ER-associated degradation (ERAD) pathway (PubMed: 26951174). When the proteasome is inhibited or the cell undergoes severe ER stress, BOK accumulates and triggers apoptosis by inducing mitochondrial outer membrane permeabilization (MOMP) or by acting directly at the ER membrane to release calcium (PubMed: 24362264). In clinical oncology, the BOK gene is frequently found to be deleted in various human cancers, including ovarian and colorectal carcinomas, suggesting it functions as a significant tumor suppressor (NCBI Gene: 666). While BOK is a compelling target for reactivating cell death in apoptosis-resistant tumors, it remains largely insensitive to current BH3 mimetics like Venetoclax, which target BCL-2 or MCL-1. Consequently, therapeutic strategies often focus on indirect modulation, such as using proteasome inhibitors like Bortezomib to stabilize BOK levels and promote cancer cell death (PubMed: 28416133).

Other names

BCL2L9BOKLhBOKBcl-2-like protein 9

Induction of mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release; induction of endoplasmic reticulum-mediated apoptosis.