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Sorting out functions of sirtuins in cancer

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Abstract

The sirtuins (SIRT 1–7) comprise a family of NAD+-dependent protein-modifying enzymes with activities in lysine deacetylation, adenosinediphospho(ADP)-ribosylation, and/or deacylation. These enzymes are involved in the cell’s stress response systems and in regulating gene expression, DNA damage repair, metabolism and survival. Sirtuins have complex roles in both promoting and/or suppressing tumorigenesis. This review presents recent research progress concerning sirtuins and cancer. On one hand, functional loss of sirtuin genes, particularly SIRT1, involved in maintaining genome integrity and DNA repair will promote tumorigenesis because of genomic instability upon their loss. On the other hand, cancer cells tend to require sirtuins for these same processes to allow them to survive, proliferate, repair the otherwise catastrophic genomic events and evolve. The bifurcated roles of SIRT1, and perhaps several other sirtuins, in cancer may be in part a result of the nature of the genes that are involved in the cell’s genome maintenance systems. The in-depth understanding of sirtuin functions may have significant implication in designing precise modulation of selective sirtuin members to aid cancer prevention or treatment under defined conditions.

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Acknowledgements

We thank the research support from the National Cancer Institute of the National Institutes of Health under award number R01 CA143421, and the State of California Tobacco Related Disease Research Program (TRDRP) award 20XT-0121 to WYC. The contents are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health.

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Roth, M., Chen, W. Sorting out functions of sirtuins in cancer. Oncogene 33, 1609–1620 (2014). https://doi.org/10.1038/onc.2013.120

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