Author/Authors :
Kim، نويسنده , , Hyun-Seok and Vassilopoulos، نويسنده , , Athanassios and Wang، نويسنده , , Rui-Hong and Lahusen، نويسنده , , Tyler and Xiao، نويسنده , , Zhen and Xu، نويسنده , , Xiaoling and Li، نويسنده , , Cuiling and Veenstra، نويسنده , , Timothy D. and Li، نويسنده , , Bing and Yu، نويسنده , , Hongtao and Ji، نويسنده , , Junfang and Wang، نويسنده , , Xin Wei and Park، نويسنده , , Seong-Hoon and Cha، نويسنده , , Yong I. and Gius، نويسنده , , David and Deng، نويسنده , , Chu-Xia، نويسنده ,
Abstract :
Summary
s 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, 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.
