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Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

Oncogene volume 28, pages 128–139 (2009)Cite this article

Abstract

The Akt signaling pathway activity increases as normal tissue progresses to malignant transformation, and regulates the translation of specific messenger RNAs (mRNAs) through multiple mechanisms. We have identified one such mechanism of Akt-dependent translation control as involving the lupus autoantigen La. La is an RNA-associated protein that contains multiple trafficking elements to support the interaction with RNAs in different subcellular locations. We show here that the La protein is a direct target of the serine/threonine protein kinase Akt on threonine 301, and La nuclear export in mouse glial progenitors, as well as its association with polysomes is modulated by Akt activity. Using a functional approach to determine the network of genes affected by La in the cytoplasm by microarray analysis of polysome-bound mRNAs, we found that La binds 34% of the polysome bound mRNAs and regulates the expression of a specific pool of mRNAs under KRas/Akt activation. Therefore, La appears to be an important contributor to Akt-mediated translational regulation of these transcripts in murine glial cells.

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Acknowledgements

We thank Dr Agnes Viale and the members of the Genomic Core Facility (MSKCC) for generation of Affymetrix data, Yelena Lyustikman for reading of the manuscript and Gloria Curto-Gonzalez, Elena Fomchenko and Hiro Momota for discussion and technical suggestions. We also thank Keryx Biopharmaceuticals for generously providing us with perifosine. This work was supported by a National Institutes of Health Grant (UO1CA04002).

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Authors and Affiliations

  1. Department of Cancer Biology and Genetics, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    F Brenet & E C Holland

  2. Computational Biology Center, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    N D Socci

  3. Department of Biochemistry, McGill University, Promenade Sir William Osler, Montreal, Quebec, Canada

    N Sonenberg

  4. Departments of Surgery, Neurosurgery and Neurology, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    E C Holland

  5. Brain Tumor Center, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    E C Holland

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  1. F Brenet
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Correspondence to F Brenet.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Brenet, F., Socci, N., Sonenberg, N. et al. Akt phosphorylation of La regulates specific mRNA translation in glial progenitors. Oncogene 28, 128–139 (2009). https://doi.org/10.1038/onc.2008.376

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