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Updated: May 14, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Intracellular localization of the BCL-2 family member BOK and functional implications
N Echeverry1, D Bachmann, F Ke
1Institute of Pharmacology, University of Bern, Bern, Switzerland.
Abstract:
The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a 'tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.
Insights
The pro-apoptotic protein BOK, a BCL-2 family member, activates mitochondrial apoptosis in a BAX/BAK-dependent manner. BOK localizes to the Golgi and ER, suggesting these organelles are key sites for its tumor suppressor functions.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- BOK is a pro-apoptotic BCL-2 family member.
- BOK resembles BAX and BAK in amino acid sequence.
- BOK is hypothesized to be a tumor suppressor due to frequent genomic deletions in cancer.
Purpose of the Study:
- To investigate the molecular functions of BOK.
- To determine the localization and role of BOK in apoptosis.
- To elucidate the relationship between BOK, BAX, and BAK in cell death.
Main Methods:
- Enforced expression of BOK in cells with varying BAX/BAK status.
- Analysis of BOK localization using microscopy.
- Assessment of cell viability and organelle integrity upon BOK overexpression.
- Evaluation of BOK-deficient cell response to Golgi/ER stress.
Main Results:
- Enforced BOK expression activates the intrinsic apoptotic pathway in BAX/BAK-proficient cells.
- BOK fails to induce apoptosis in cells lacking BAX and BAK.
- BOK localizes to and inserts into Golgi and ER membranes via its C-terminal transmembrane domain.
- BOK overexpression leads to early fragmentation of Golgi and ER compartments.
- Bok-deficient cells exhibit abnormal responses to brefeldin A, a Golgi/ER stressor.
Conclusions:
- BOK induces apoptosis in a BAX/BAK-dependent manner.
- Major functions of BOK are associated with the Golgi and ER membranes.
- BOK likely acts as a tumor suppressor through its functions at the Golgi and ER.
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