DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis.
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.
Marash
Lea
L
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Liberman
Noa
N
Henis-Korenblit
Sivan
S
Sivan
Gilad
G
Reem
Eran
E
Elroy-Stein
Orna
O
Kimchi
Adi
A
D020121:5' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D010448:Peptide Initiation Factors; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
D020121:5' Untranslated Regions; C113920:EIF4G1 protein, human; C491300:EIF4G2 protein, human; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D019253:Proto-Oncogene Proteins c-bcl-2; C104836:eukaryotic translational regulator p97; D016203:CDC2 Protein Kinase