Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1

S. Shin, L. Wolgamott, J. Tcherkezian, S. Vallabhapurapu, Y. Yu, P. P. Roux, S. O. Yoon

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Protein synthesis has a key role in the control of cell proliferation, and its deregulation is associated with pathological conditions, notably cancer. Rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1), was known to inhibit protein synthesis. However, it does not substantially inhibit protein synthesis and cell proliferation in many cancer types. We were interested in finding a novel target in rapamycin-resistant cancer. The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1). Here, we provide evidence that glycogen synthase kinase (GSK)-3β promotes cell proliferation through positive regulation of protein synthesis. We found that GSK-3β phosphorylates and inactivates 4E-BP1, thereby increasing eIF4E-dependent protein synthesis. Considering the clinical relevance of pathways regulating protein synthesis, our study provides a promising new strategy and target for cancer therapy.

Original languageEnglish (US)
Pages (from-to)1690-1699
Number of pages10
JournalOncogene
Volume33
Issue number13
DOIs
StatePublished - Mar 27 2014

Keywords

  • 4E-BP1
  • GSK-3
  • Translation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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