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DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis.| Authors: | Lea Marash, Noa Liberman, Sivan Henis-Korenblit, Gilad Sivan, Eran Reem, Orna Elroy-Stein, Adi Kimchi | | Language: | Eng. | | Date: | 23-05-2008 | | Journal: |
(1097-4164)
| | Release: | Mol Cell. 2008 May;30(4):447-59 | |
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Abstract:
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DAP5 is an eIF4G protein previously implicated in mediating cap-independent translation in response to cellular stresses. Here we report that DAP5 is crucial for continuous cell survival in nonstressed cells. The knockdown of endogenous DAP5 induced M phase-specific caspase-dependent apoptosis. Bcl-2 and CDK1 were identified by two independent screens as DAP5 translation targets. Notably, the activity of the Bcl-2 IRES was reduced in DAP5 knockdown cells and a selective shift of Bcl-2 mRNA toward light polysomal fractions was detected. Furthermore, a functional IRES was identified in the 5'UTR of CDK1. At the cellular level, attenuated translation of CDK1 by DAP5 knockdown decreased the phosphorylation of its M phase substrates. Ectopic expression of Bcl-2 or CDK1 proteins partially reduced the extent of caspase activation caused by DAP5 knockdown. Thus, DAP5 is necessary for maintaining cell survival during mitosis by promoting cap-independent translation of at least two prosurvival proteins.
| | Copyright: |
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. | | Full text: |  EBSCO - HTML (needs subscription) | | Terms: | 5' Untranslated Regions, Animals, Apoptosis, CDC2 Protein Kinase, Cell Line, Cell Survival, Eukaryotic Initiation Factor-4G, Humans, Mice, Mitosis, Peptide Initiation Factors, Polyribosomes, Protein Biosynthesis, Proto-Oncogene Proteins c-bcl-2, RNA Interference | | |
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