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

Article Details

Citation

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

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.

PubMed ID
22014574 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Aurora kinase AO14965Details
NAD-dependent protein deacetylase sirtuin-2Q8IXJ6Details