Journal
CELL DEATH AND DIFFERENTIATION
Volume 17, Issue 11, Pages 1672-1683Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.97
Keywords
apoptosis; Bcl-2 family; BH3-only proteins; Bmf
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Funding
- AICR, St. Andrews, UK [06-0440]
- Austrian Science Fund (FWF) [SFB021]
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Tight transcriptional regulation, alternative splicing and/or post-translational modifications of BH3-only proteins fine-tune their proapoptotic function. In this study, we characterize the gene locus of the BH3-only protein Bmf (Bcl-2-modifying factor) and describe the generation of two major isoforms from a common transcript in which initiation of protein synthesis involves leucine-coding CUG. Bmf(CUG) and the originally described isoform, Bmf-short, display comparable binding affinities to prosurvival Bcl-2 family members, localize preferentially to the outer mitochondrial membrane and induce rapid Bcl-2-blockable apoptosis. Notably, endogenous Bmf expression is induced on forms of cell stress known to cause repression of the CAP-dependent translation machinery such as serum deprivation, hypoxia, inhibition of the PI3K/AKT pathway or mTOR, as well as direct pharmacological inhibition of the eukaryotic translation initiation factor elF-4E. Knock down or deletion of Bmf reduces apoptosis under some of these conditions, demonstrating that Bmf can act as a sentinel for stress-impaired CAP-dependent protein translation machinery. Cell Death and Differentiation (2010) 17, 1672-1683; doi:10.1038/cdd.2010.97; published online 13 August 2010
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