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Article Dans Une Revue Cell Death and Differentiation Année : 2010

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

Résumé

Tight transcriptional regulation, post-translational modifications and/or alternative splicing of BH3-only proteins fine-tune their pro-apoptotic function. Here, 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 where initiation of protein synthesis involves leucine-coding CUG. BmfCUG and the originally described isoform, Bmf short (BmfS), display comparable binding affinities to pro-survival Bcl-2 family members, localize preferentially to the outer mitochondrial membrane and induce rapid Bcl-2-blockable apoptosis. Notably, endogenous Bmf expression is induced upon forms of cell stress known to cause the 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 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 the stress-impaired CAP-dependent protein translation machinery.

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Dates et versions

hal-00565453 , version 1 (13-02-2011)

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Andreas Villunger, Francesca Grespi, Claudia Soratroi, Gerhard Krumschnabel, Benedicte Sohm, et al.. BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.97⟩. ⟨hal-00565453⟩

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