DAP5 Promotes Cap-Independent Translation of Bcl-2 and CDK1 to Facilitate Cell Survival during Mitosis

Lea Marash, Noa Liberman, Sivan Henis-Korenblit, Gilad Sivan, Eran Reem, Orna Elroy-Stein, Adi Kimchi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)447-459
Number of pages13
JournalMolecular Cell
Volume30
Issue number4
DOIs
StatePublished - 23 May 2008

Keywords

  • CELLCYCLE
  • RNA

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