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

karmarks 添加于 2011-10-22 16:24 | 2036 次阅读 | 0 个评论

作者
Kim H-S, Vassilopoulos A, Wang R-H, Lahusen T, Xiao Z, Xu X, Li C, Veenstra T D, Li B, Yu H, Ji J, Wang X W, Park S-H, Cha Y I, Gius D, Deng C-X
摘要
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.
详细资料
- 文献种类:期刊
- 期刊名称: Cancer Cell
- 期刊缩写: Cancer Cell
- 期卷页: 2011年第20卷第4期 487-499页
- ISBN: 1535-6108
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附件
SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating
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