DBC1对SUV39H1甲基转移酶活性的抑制作用。
Inhibition of SUV39H1 methyltransferase activity by DBC1.
作者信息
Li Zhenyu, Chen Lihong, Kabra Neha, Wang Chuangui, Fang Jia, Chen Jiandong
机构信息
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
出版信息
J Biol Chem. 2009 Apr 17;284(16):10361-6. doi: 10.1074/jbc.M900956200. Epub 2009 Feb 13.
SUV39H1 is a histone H3K9-specific methyltransferase important for heterochromatin formation, regulation of gene expression, and induction of senescence in premalignant cells. SUV39H1 forms a complex with SirT1, and its activity is stimulated by SirT1 binding. Here we present evidence that the product of the DBC1 (deleted in breast cancer 1) gene disrupts the SUV39H1-SirT1 complex. Furthermore, DBC1 binds to the SUV39H1 catalytic domain and inhibits its ability to methylate histone H3 in vitro and in vivo. Knockdown of endogenous DBC1 increased the level of cellular H3K9 methylation. As expected, DBC1 also binds to SirT1 and inhibits the deacetylase activity of SirT1. These results identify DBC1 as a novel cellular inhibitor of SUV39H1 activity. DBC1 may be an important regulator of heterochromatin formation and genomic stability by disrupting the SUV39H1-SirT1 complex and inactivating both enzymes.
SUV39H1是一种组蛋白H3K9特异性甲基转移酶，对异染色质形成、基因表达调控以及癌前细胞衰老的诱导至关重要。SUV39H1与SirT1形成复合物，其活性受SirT1结合的刺激。在此我们提供证据表明，乳腺癌缺失基因1（DBC1）的产物会破坏SUV39H1 - SirT1复合物。此外，DBC1与SUV39H1催化结构域结合，并在体外和体内抑制其甲基化组蛋白H3的能力。敲低内源性DBC1会增加细胞H3K9甲基化水平。正如预期的那样，DBC1也与SirT1结合并抑制SirT1的去乙酰化酶活性。这些结果确定DBC1是SUV39H1活性的一种新型细胞抑制剂。通过破坏SUV39H1 - SirT1复合物并使这两种酶失活，DBC1可能是异染色质形成和基因组稳定性的重要调节因子。
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