Regulation of TET protein stability by calpains.

Regulation of TET protein stability by calpains.
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DOI:
10.1016/j.celrep.2013.12.031
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发表时间:
2014-01-30
期刊:
影响因子:
8.8
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学1区
文献类型:
--
作者:
Wang Y;Zhang Y

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胞嘧啶5位甲基化(5mC)是一种重要的表观遗传修饰,影响染色质结构和基因表达。最近的研究已经确定了10 - 11易位(Tet)家族蛋白在调节DNA甲基化动力学中的关键功能。在哺乳动物中已经鉴定出三种Tet基因,它们都编码能够氧化5mC的蛋白质,作为DNA去甲基化过程的一部分。虽然Tet在转录水平上的表达调控已被充分记录,但Tet蛋白如何在翻译后水平上被调控却知之甚少。在这项研究中,我们报告了所有三种TET蛋白都是钙蛋白酶家族的直接底物。具体来说,calpain1介导小鼠ES细胞中TET1和TET2的转换,calpain2调节分化过程中TET3的水平。这项研究提供了TET蛋白受calpain介导的降解的第一个证据。
DNA methylation at the fifth position of cytosine (5mC) is an important epigenetic modification that affects chromatin structure and gene expression. Recent studies have established a critical function of the Ten-eleven translocation (Tet) family of proteins in regulating DNA methylation dynamics. Three Tet genes have been identified in mammals, and they all encode for proteins capable of oxidizing 5mC as part of the DNA demethylation process. While regulation of Tet expression at the transcriptional level is well documented, how TET proteins are regulated at post-translational level is poorly understood. In this study, we report that all three TET proteins are direct substrates of calpains, a family of calcium-dependent proteases. Specifically, calpain1 mediates TET1 and TET2 turnover in mouse ES cells, and calpain2 regulates TET3 level during differentiation. This study provides the first evidence that TET proteins are subject to calpain-mediated degradation.
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