Intracellular localization of the BCL-2 family member BOK and functional implications

Echeverry, Nohemy; Bachmann, Daniel; Ke, Francine; Strasser, Andreas; Simon, Hans-Uwe; Kaufmann, Thomas (2013). Intracellular localization of the BCL-2 family member BOK and functional implications. Cell death and differentiation, 20(6), pp. 785-799. Nature Publishing Group 10.1038/cdd.2013.10

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Echeverry, Nohemy; Bachmann, Daniel; Simon, Hans-Uwe and Kaufmann, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1350-9047

Publisher:

Nature Publishing Group

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Anita Dähler

Date Deposited:

06 Dec 2013 03:37

Last Modified:

24 Oct 2019 06:41

Publisher DOI:

10.1038/cdd.2013.10

PubMed ID:

23429263

Uncontrolled Keywords:

apoptosis; BOK; BAX/BAK; tail-anchor; Golgi; ER

BORIS DOI:

10.7892/boris.39534

URI:

https://boris.unibe.ch/id/eprint/39534

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