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

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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

References

  • Aoki M, Batista O, Bellacosa A, Tsichlis P, Vogt PK . (1998). The Akt kinase: molecular determinants of oncogenicity. Proc Natl Acad Sci USA 95: 14950–14955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aoki M, Blazek E, Vogt PK . (2001). A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc Natl Acad Sci USA 98: 136–141.

    Article  CAS  PubMed  Google Scholar 

  • Aoki M, Schetter C, Himly M, Batista O, Chang HW, Vogt PK . (2000). The catalytic subunit of phosphoinositide 3-kinase: requirements for oncogenicity. J Biol Chem 275: 6267–6275.

    Article  CAS  PubMed  Google Scholar 

  • Bader AG, Felts KA, Jiang N, Chang HW, Vogt PK . (2003). Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway. Proc Natl Acad Sci USA 100: 12384–12389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bader AG, Kang S, Zhao L, Vogt PK . (2005). Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 5: 921–929.

    Article  CAS  PubMed  Google Scholar 

  • Bader AG . (2006). YB-1 activities in oncogenesis: transcription and translation. Curr Cancer Ther Rev 2: 31–39.

    Article  CAS  Google Scholar 

  • Bader AG, Vogt PK . (2005). Inhibition of protein synthesis by Y box-binding protein 1 blocks oncogenic cell transformation. Mol Cell Biol 25: 2095–2106.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Basaki Y, Hosoi F, Oda Y, Fotovati A, Maruyama Y, Oie S et al. (2006). Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Oncogene 26: 2736–2746.

    Article  PubMed  Google Scholar 

  • Bergmann S, Royer-Pokora B, Fietze E, Jurchott K, Hildebrandt B, Trost D et al. (2005). YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification. Cancer Res 65: 4078–4087.

    Article  CAS  PubMed  Google Scholar 

  • Bouvet P, Matsumoto K, Wolffe AP . (1995). Sequence-specific RNA recognition by the xenopus Y-box proteins. An essential role for the cold shock domain. J Biol Chem 270: 28297–28303.

    Article  CAS  PubMed  Google Scholar 

  • Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN et al. (1997). Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 276: 1848–1850.

    Article  CAS  PubMed  Google Scholar 

  • Evdokimova V, Ruzanov P, Anglesio MS, Sorokin AV, Ovchinnikov LP, Buckley J et al. (2006). Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Mol Cell Biol 26: 277–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evdokimova V, Ruzanov P, Imataka H, Raught B, Svitkin Y, Ovchinnikov LP et al. (2001). The major mRNA-associated protein YB-1 is a potent 5′ cap-dependent mRNA stabilizer. EMBO J 20: 5491–5502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jurchott K, Bergmann S, Stein U, Walther W, Janz M, Manni I et al. (2003). YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression. J Biol Chem 278: 27988–27996.

    Article  PubMed  Google Scholar 

  • Kloks CP, Spronk CA, Lasonder E, Hoffmann A, Vuister GW, Grzesiek S et al. (2002). The solution structure and DNA-binding properties of the cold-shock domain of the human Y-box protein YB-1. J Mol Biol 316: 317–326.

    Article  CAS  PubMed  Google Scholar 

  • Minich WB, Ovchinnikov LP . (1992). Role of cytoplasmic mRNP proteins in translation. Biochimie 74: 477–483.

    Article  CAS  PubMed  Google Scholar 

  • Sorokin AV, Selyutina AA, Skabkin MA, Guryanov SG, Nazimov IV, Richard C et al. (2005). Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response. EMBO J 24: 3602–3612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stenina OI, Shaneyfelt KM, DiCorleto PE . (2001). Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation. Proc Natl Acad Sci USA 98: 7277–7282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutherland BW, Kucab J, Wu J, Lee C, Cheang MC, Yorida E et al. (2005). Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. Oncogene 24: 4281–4292.

    Article  CAS  PubMed  Google Scholar 

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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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