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Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

Oncogene volume 29, pages 4378–4387 (2010)Cite this article

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Abstract

The p53 protein is the most studied tumor suppressor and the p53 pathway has been shown to mediate cellular stress responses that are disrupted when cancer develops. After DNA damage, p53 is activated as transcription factor to directly induce the expression of target genes involved in cell-cycle arrest, DNA repair, senescence and, importantly, apoptosis. Post-translational modifications of p53 are essential for the activation of p53 and for selection of target genes. The tumor suppressor homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating its N-terminal serine 46 (Ser46) and facilitating Lys382 acetylation at the C-terminus. HIPK2 is activated by numerous genotoxic agents and can be deregulated in tumors by several conditions including hypoxia. Recent findings suggest that HIPK2 active/inactive protein can affect p53 function in multiple and unexpected ways. This makes p53 as well as HIPK2 interesting targets for cancer therapy. Hence, understanding the role of HIPK2 as p53 activator may provide important insights in the process of tumor progression, and may also serve as the crucial point in the diagnostic and therapeutical aspects of cancer.

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Acknowledgements

This research conducted in our laboratory is supported by Grants from Italian Association for Cancer Research and from University ‘Gd’Annunzio’. RP is a recipient of a fellowship from Italian Foundation for Cancer Research (FIRC).

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  1. Department of Experimental Oncology, Molecular Oncogenesis Laboratory, National Cancer Institute Regina Elena, Rome, Italy

    R Puca, L Nardinocchi & G D'Orazi

  2. Department of Oncology and Neurosciences, University ‘G. d’Annunzio’, Chieti, Italy

    R Puca, L Nardinocchi & G D'Orazi

  3. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    D Givol

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Puca, R., Nardinocchi, L., Givol, D. et al. Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells. Oncogene 29, 4378–4387 (2010). https://doi.org/10.1038/onc.2010.183

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