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. © 2008 Elsevier Inc. All rights reserved.
Marash, L., Liberman, N., Henis-Korenblit, S., Sivan, G., Reem, E., Elroy-Stein, O., & Kimchi, A. (2008). DAP5 Promotes Cap-Independent Translation of Bcl-2 and CDK1 to Facilitate Cell Survival during Mitosis. Molecular Cell, 30(4), 447–459. https://doi.org/10.1016/j.molcel.2008.03.018