2. Academic Validation
  3. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity

SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity

  • Cancer Cell. 2011 Oct 18;20(4):487-99. doi: 10.1016/j.ccr.2011.09.004.
Hyun-Seok Kim 1,  Athanassios Vassilopoulos,  Rui-Hong Wang,  Tyler Lahusen,  Zhen Xiao,  Xiaoling Xu,  Cuiling Li,  Timothy D Veenstra,  Bing Li,  Hongtao Yu,  Junfang Ji,  Xin Wei Wang,  Seong-Hoon Park,  Yong I Cha,  David Gius,  Chu-Xia Deng
Affiliations

Affiliation

  • 1 Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
PMID: 22014574 DOI: 10.1016/j.ccr.2011.09.004
Abstract

Members of Sirtuin family regulate multiple critical biological processes, yet their role in carcinogenesis remains controversial. To investigate the physiological functions of SIRT2 in development and tumorigenesis, we disrupted SIRT2 in mice. We demonstrated that SIRT2 regulates the anaphase-promoting complex/cyclosome activity through deacetylation of its coactivators, APC(CDH1) and CDC20. SIRT2 deficiency caused increased levels of mitotic regulators, including Aurora-A and -B that direct centrosome amplification, aneuploidy, and mitotic cell death. Sirt2-deficient mice develop gender-specific tumorigenesis, with females primarily developing mammary tumors, and males developing more hepatocellular carcinoma (HCC). Human breast cancers and HCC samples exhibited reduced SIRT2 levels compared with normal tissues. These data demonstrate that SIRT2 is a tumor suppressor through its role in regulating mitosis and genome integrity.

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