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BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis.


ABSTRACT: 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 eIF-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.

SUBMITTER: Grespi F 

PROVIDER: S-EPMC2953534 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis.

Grespi F F   Soratroi C C   Krumschnabel G G   Sohm B B   Ploner C C   Geley S S   Hengst L L   Häcker G G   Villunger A A  

Cell death and differentiation 20100813 11


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 pr  ...[more]

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