SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity

Hyun Seok Kim, 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

Research output: Contribution to journalArticle

284 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)487-499
Number of pages13
JournalCancer Cell
Volume20
Issue number4
DOIs
StatePublished - Oct 18 2011

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Carcinogenesis
Genome
Breast Neoplasms
Hepatocellular Carcinoma
Anaphase-Promoting Complex-Cyclosome
Biological Phenomena
Centrosome
Aneuploidy
Mitosis
Cell Death
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Kim, H. S., Vassilopoulos, A., Wang, R. H., Lahusen, T., Xiao, Z., Xu, X., ... Deng, C. X. (2011). SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. Cancer Cell, 20(4), 487-499. https://doi.org/10.1016/j.ccr.2011.09.004

SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. / Kim, Hyun Seok; Vassilopoulos, Athanassios; Wang, Rui Hong; Lahusen, Tyler; Xiao, Zhen; Xu, Xiaoling; Li, Cuiling; Veenstra, Timothy D.; Li, Bing; Yu, Hongtao; Ji, Junfang; Wang, Xin Wei; Park, Seong Hoon; Cha, Yong I.; Gius, David; Deng, Chu Xia.

In: Cancer Cell, Vol. 20, No. 4, 18.10.2011, p. 487-499.

Research output: Contribution to journalArticle

Kim, HS, Vassilopoulos, A, Wang, RH, Lahusen, T, Xiao, Z, Xu, X, Li, C, Veenstra, TD, Li, B, Yu, H, Ji, J, Wang, XW, Park, SH, Cha, YI, Gius, D & Deng, CX 2011, 'SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity', Cancer Cell, vol. 20, no. 4, pp. 487-499. https://doi.org/10.1016/j.ccr.2011.09.004
Kim, Hyun Seok ; Vassilopoulos, Athanassios ; Wang, Rui Hong ; Lahusen, Tyler ; Xiao, Zhen ; Xu, Xiaoling ; Li, Cuiling ; Veenstra, Timothy D. ; Li, Bing ; Yu, Hongtao ; Ji, Junfang ; Wang, Xin Wei ; Park, Seong Hoon ; Cha, Yong I. ; Gius, David ; Deng, Chu Xia. / SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. In: Cancer Cell. 2011 ; Vol. 20, No. 4. pp. 487-499.
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