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首页> 外文期刊>Cancer Cell >SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity.
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SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity.

机译：SIRT2通过调节APC / C活性来维持基因组完整性并抑制肿瘤发生。

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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.
机译：瑟土因家族成员调控着多种关键的生物学过程，但是它们在致癌作用中的作用仍存在争议。为了研究SIRT2在发育和肿瘤发生中的生理功能，我们破坏了小鼠的Sirt2。我们证明了SIRT2通过其辅助活化剂APC（CDH1）和CDC20的脱乙酰作用来调节后期促进复合物/环体的活性。 SIRT2缺乏引起有丝分裂调节剂水平升高，包括指导中心体扩增，非整倍性和有丝分裂细胞死亡的Aurora-A和-B。 Sirt2缺陷型小鼠会发生性别特异性肿瘤发生，雌性主要发生乳腺肿瘤，而雄性则发展更多的肝细胞癌（HCC）。与正常组织相比，人乳腺癌和HCC样品的SIRT2水平降低。这些数据表明，SIRT2通过调节有丝分裂和基因组完整性而发挥抑癌作用。

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