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A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity

Oncogene volume 35, pages 4949–4956 (2016)Cite this article

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Abstract

Sirt6 is a histone deacetylase with NAD+-dependent activity. Sirt6 has been shown as a tumor suppressor partially via inhibiting the expression of c-Myc target genes and ribosome biogenesis. However, how to regulate Sirt6 activity is largely unknown. In this study, we identify that Sirt6 can be modified by small ubiquitin-like modifier. Sirt6 SUMOylation deficiency specifically decreases its deacetylation of H3K56 but not H3K9 in vivo. Mechanistically, we find that SUMOylation deficiency decreases Sirt6 binding with c-Myc, decreasing Sirt6 occupancy on the locus of c-Myc target genes. Therefore, Sirt6 SUMOylation deficiency reduces its deacetylation of H3k56 and its repression of c-Myc target genes. Moreover, Sirt6 SUMOylation deficiency reduces its suppression of cell proliferation and tumorigenesis. Thus, these results reveal that SUMOylation has an important role in regulation of Sirt6 deacetylation on H3K56, as well as its tumor suppressive activity.

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Acknowledgements

We thank Dr Chuxia Deng (NIH, Bethesda, MD, USA) for kindly providing for Sirt6−/− MEF cells. This work was supported by National Basic Research Program of China (973 Program; no. 2013CB910902 to JC), National Natural Science Foundation of China (91229202 and 81430069 to JC).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    J Cai, Y Zuo, T Wang, Y Cao, R Cai & J Cheng

  2. Shanghai Third People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China

    F-L Chen

  3. Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China

    J Mu

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  1. J Cai
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  2. Y Zuo
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Correspondence to J Cheng or J Mu.

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Cai, J., Zuo, Y., Wang, T. et al. A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity. Oncogene 35, 4949–4956 (2016). https://doi.org/10.1038/onc.2016.24

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  • DOI: https://doi.org/10.1038/onc.2016.24

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