Phosphorylation by Akt disables the anti-oncogenic activity of YB-1

Oncogene. 2008 Feb 14;27(8):1179-82. doi: 10.1038/sj.onc.1210719. Epub 2007 Aug 20.


The Y box-binding protein 1 (YB-1) is a DNA/RNA-binding protein that regulates mRNA transcription and translation. It is a major component of free messenger ribonucleoprotein particles and, at higher concentrations, blocks protein synthesis. In chicken embryo fibroblasts, overexpression of YB-1 confers a specific resistance to oncogenic cellular transformation by phosphoinositide 3-kinase (PI3K) or Akt/PKB. Recent studies have identified YB-1 as a direct substrate of Akt. The functional significance of Akt-mediated phosphorylation remains largely unknown. We generated YB-1 mutants in the Akt phosphorylation consensus sequence to explore the effect of phosphorylated YB-1 in PI3K-induced transformation. In contrast to wild-type YB-1, the phosphomimetic S99E mutant no longer interferes with cellular transformation. This mutant has reduced affinity for the cap of mRNAs and fails to inhibit cap-dependent translation. The data suggest that phosphorylation by Akt disables the inhibitory activity of YB-1 and thereby enhances the translation of transcripts that are necessary for oncogenesis. Overexpression of wild-type YB-1 overrides inactivation by Akt and maintains inhibition of protein synthesis and resistance to transformation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • Chick Embryo
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / physiology*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Tumor Suppressor Proteins / antagonists & inhibitors*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Y-Box-Binding Protein 1 / antagonists & inhibitors*
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*


  • RNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Y-Box-Binding Protein 1
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt