Intracellular localization of the BCL-2 family member BOK and functional implications
- Author(s)
- Echeverry, N; Bachmann, D; Ke, F; Strasser, A; Simon, HU; Kaufmann, T;
- Details
- Publication Year 2013-06,Volume 20,Issue #6,Page 785-799
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- MITOCHONDRIAL OUTER-MEMBRANE; UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; CELL-DEATH; BH3-ONLY PROTEINS; PROAPOPTOTIC BAX; MAMMALIAN-CELLS; BH3 DOMAIN; ER STRESS; IN-VITRO
- Research Division(s)
- Molecular Genetics Of Cancer
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647236/
- Publisher's Version
- https://doi.org/10.1038/cdd.2013.10
- NHMRC Grants
- NHMRC/1020363, NHMRC/1016701,
- Terms of Use/Rights Notice
- © 2013 ADMC Associazione Differenziamento e Morte Cellulare
Creation Date: 2013-06-01 12:00:00