Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival Academic Article uri icon

Overview

MeSH Major

  • Deoxycytidine
  • Drug Resistance, Neoplasm
  • Glucose
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mucin-1
  • Pancreatic Neoplasms

abstract

  • The protein kinase maternal and embryonic leucine zipper kinase (MELK) is critical for mitotic progression of cancer cells; however, its mechanisms of action remain largely unknown. By combined approaches of immunoprecipitation/mass spectrometry and peptide library profiling, we identified the eukaryotic translation initiation factor 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most robust in the mitotic phase of the cell cycle. We further show that the MELK-eIF4B signaling axis regulates protein synthesis during mitosis. Specifically, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our study thus defines a MELK-eIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival.

publication date

  • August 30, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5024598

Digital Object Identifier (DOI)

  • 10.1073/pnas.1606862113

PubMed ID

  • 27528663

Additional Document Info

start page

  • 9810

end page

  • 5

volume

  • 113

number

  • 35