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
中科院分区:
文献类型:
--
作者:
Wang Y;Zhang Y
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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