| First Author | Grespi F | Year | 2010 |
| Journal | Cell Death Differ | Volume | 17 |
| Issue | 11 | Pages | 1672-83 |
| PubMed ID | 20706276 | Mgi Jnum | J:186983 |
| Mgi Id | MGI:5433846 | Doi | 10.1038/cdd.2010.97 |
| Citation | Grespi F, et al. (2010) BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell Death Differ 17(11):1672-83 |
| abstractText | 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. |
