SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity.
SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity.
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DOI：
10.1016/j.ccr.2011.09.004
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发表时间：
2011-10-18
期刊：
影响因子：
50.3
通讯作者：
Deng CX
中科院分区：
文献类型：
--
作者：
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
sirtuin家族成员调节多种重要的生物学过程，但其在肿瘤发生中的作用仍存在争议。为了研究SIRT 2在发育和肿瘤发生中的生理功能，我们在小鼠中破坏了Sirt 2。我们证明了SIRT 2通过其共激活剂APCCDH 1和CDC 20的脱乙酰化来调节后期促进复合物/环体活性。SIRT 2缺陷导致有丝分裂调节因子水平增加，包括Aurora-A和-B，它们指导中心体扩增、非整倍性和有丝分裂细胞死亡。Sirt 2缺陷小鼠发生性别特异性肿瘤，雌性主要发生乳腺肿瘤，雄性发生更多肝细胞癌（HCC）。与正常组织相比，人类乳腺癌和HCC样品表现出降低的SIRT 2水平。这些数据表明，SIRT 2是一种肿瘤抑制因子，通过其调节有丝分裂和基因组完整性的作用。
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 co-activators, APCCDH1 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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影响因子：
5.3
作者：
Lee, Ho;Lee, Dong Jun;Lim, Dae-Sik
通讯作者：
Lim, Dae-Sik
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
11.2
作者：
Iwanaga, Yoichi;Chi, Ya-Hui;Jeang, Kuan-Teh
通讯作者：
Jeang, Kuan-Teh
影响因子：
5.3
作者：
Cowley, Dale O.;Rivera-Perez, Jaime A.;Van Dyke, Terry
通讯作者：
Van Dyke, Terry
DOI：
10.1073/pnas.0913668107
发表时间：
2010-01-12
影响因子：
11.1
作者：
Almeida, Angeles;Bolanos, Juan P.;Moncada, Salvador
通讯作者：
Moncada, Salvador