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KATs in cancer: functions and therapies

Oncogene volume 34, pages 4901–4913 (2015)Cite this article

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Abstract

Post-translational acetylation of lysines is most extensively studied in histones, but this modification is also found in many other proteins and is implicated in a wide range of biological processes in both the cell nucleus and the cytoplasm. Like phosphorylation, acetylation patterns and levels are often altered in cancer, therefore small molecule inhibition of enzymes that regulate acetylation and deacetylation offers much potential for inhibiting cancer cell growth, as does disruption of interactions between acetylated residues and ‘reader’ proteins. For more than a decade now, histone deacetylase inhibitors have been investigated for their ability to increase acetylation and promote expression of tumor suppressor genes. However, emerging evidence suggests that acetylation can also promote cancer, in part by enhancing the functions of oncogenic transcription factors. In this review, we focus on how acetylation of both histone and non-histone proteins may drive cancer, and we will discuss the implications of such changes on how patients are assigned to therapeutic agents. Finally, we will explore what the future holds in the design of small-molecule inhibitors for modulation of levels or functions of acetylation states.

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Acknowledgements

We thank Evangelia Koutelou for the critical reading of this manuscript and Andria Schibler for advice and contributions to artwork. This work was partially supported by NIH R01067718 to SYRD.

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  1. A Farria and W Li: These authors contributed equally to this work.

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  1. Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, Graduate School of Biomedical Sciences, University of Texas M.D Anderson Cancer Center Science Park, Smithville, Texas, USA

    A Farria, W Li & S Y R Dent

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Farria, A., Li, W. & Dent, S. KATs in cancer: functions and therapies. Oncogene 34, 4901–4913 (2015). https://doi.org/10.1038/onc.2014.453

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