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Regulation of tumor suppressor p53 at the RNA level

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Abstract

p53 is a key tumor suppressor that triggers cell cycle arrest, senescence, or apoptosis in response to cellular stress. Frequent p53 mutation in human tumors allows survival, sustained growth, and tumor progression. p53 is expressed at low levels under normal conditions, due to rapid protein turnover. Stress signaling induces p53 protein stabilization through phosphorylation and other post-translational modifications. However, recent studies have demonstrated critical regulation of p53 at the mRNA level, mediated via both the 5′UTR and the 3′UTR and affecting both the stability and the translation efficiency of the p53 mRNA. Both proteins and microRNAs have been implicated in such regulation. The p53 target gene Wig-1 encodes a zinc finger protein that binds to double-stranded RNA and enhances p53 mRNA stability by binding to the 3′UTR in a positive feedback loop. Here, we shall summarize current knowledge about regulation of the p53 mRNA and discuss possible implications for cancer therapy.

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Acknowledgements

The authors are supported by grants from the Swedish Cancer Society, Vetenskapsrådet (VR), The Gustaf V Jubilee Fund, The Cancer Society of Stockholm, and the Robert Lundberg Foundation.

Conflict of interest disclosure

K.G.W. is cofounder, shareholder, and board member of Aprea AB, a company that develops p53-based cancer therapy.

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Authors and Affiliations

  1. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Anna Vilborg & Klas G. Wiman

  2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Margareta T. Wilhelm

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  1. Anna Vilborg
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Correspondence to Klas G. Wiman.

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Vilborg, A., Wilhelm, M.T. & Wiman, K.G. Regulation of tumor suppressor p53 at the RNA level. J Mol Med 88, 645–652 (2010). https://doi.org/10.1007/s00109-010-0609-2

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