钙蛋白酶对TET蛋白稳定性的调控
Regulation of TET protein stability by calpains.
作者信息
Wang Yu, Zhang Yi
机构信息
Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.
Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.
出版信息
Cell Rep. 2014 Jan 30;6(2):278-84. doi: 10.1016/j.celrep.2013.12.031. Epub 2014 Jan 9.
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. Although regulation of Tet expression at the transcriptional level is well documented, how TET proteins are regulated at posttranslational 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 ESCs, and calpain2 regulates TET3 level during differentiation. This study provides evidence that TET proteins are subject to calpain-mediated degradation.
胞嘧啶第五位的DNA甲基化（5mC）是一种重要的表观遗传修饰，它影响染色质结构和基因表达。最近的研究确定了Tet蛋白家族在调节DNA甲基化动力学方面的关键功能。在哺乳动物中已鉴定出三个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在转录水平的表达调控已有充分记录，但对TET蛋白在翻译后水平的调控却知之甚少。在本研究中，我们报告所有三种TET蛋白都是钙蛋白酶（一类钙依赖性蛋白酶）的直接底物。具体而言，钙蛋白酶1介导小鼠胚胎干细胞中TET1和TET2的周转，而钙蛋白酶2在分化过程中调节TET3水平。本研究提供了证据表明TET蛋白会受到钙蛋白酶介导的降解。
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