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

Oncogene volume 27, pages 1179–1182 (2008)Cite this article

Abstract

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.

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Abbreviations

CEF:

chicken embryo fibroblasts

PI3K:

phosphoinositide 3-kinase

mRNP:

messenger ribonucleoprotein particle

PAGE:

polyacrylamide gel electrophoresis

YB-1:

Y box-binding protein 1

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Acknowledgements

We thank L Ueno for technical assistance in tissue culture. This work was supported by grants from the National Cancer Institute. This is manuscript number 18882-MEM of The Scripps Research Institute.

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  1. Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

    A G Bader & P K Vogt

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  1. A G Bader
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  2. P K Vogt
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Correspondence to A G Bader.

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Bader, A., Vogt, P. Phosphorylation by Akt disables the anti-oncogenic activity of YB-1. Oncogene 27, 1179–1182 (2008). https://doi.org/10.1038/sj.onc.1210719

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