Grespi 2010 Cell Death Differ

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Grespi F, Soratroi C, Krumschnabel G, Sohm B, Ploner C, Geley S, Hengst L, Häcker G, Villunger A (2010) BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell Death Differ 17:1672-83.

» PMID: 20706276 Open Access

Grespi F, Soratroi C, Krumschnabel G, Sohm B, Ploner C, Geley S, Hengst L, Haecker G, Villunger A (2010) Cell Death Differ

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. BmfCUG and the originally described isoform, Bmf-short (BmfS), 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.

Keywords: Apoptosis, Bcl-2 family, BH3-only proteins, Bmf


Labels:

Stress:Cell death