MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.
MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.
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MYPT1/PP1 — 介导的 EZH2 S21 去磷酸化通过控制多个基因家族促进纤维化中的上皮 — 间质转化
DOI：
10.1002/advs.202105539
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发表时间：
2022-05
期刊：
影响因子：
15.1
通讯作者：
Li, David Wan-Cheng
中科院分区：
文献类型：
--
作者：
Zhang, Lan;Wang, Ling;Hu, Xue-Bin;Hou, Min;Xiao, Yuan;Xiang, Jia-Wen;Xie, Jie;Chen, Zhi-Gang;Yang, Tian-Heng;Nie, Qian;Fu, Jia-Ling;Wang, Yan;Zheng, Shu-Yu;Liu, Yun-Fei;Gan, Yu-Wen;Gao, Qian;Bai, Yue-Yue;Wang, Jing-Miao;Qi, Rui-Li;Zou, Ming;Ke, Qin;Zhu, Xing-Fei;Gong, Lili;Liu, Yizhi;Li, David Wan-Cheng
关键词：
甲基转移酶EZH 2在调节染色质构象和基因转录中起重要作用。EZH 2在S21处被AKT激酶磷酸化抑制其功能。然而，负责EZH 2-S21去磷酸化的蛋白磷酸酶仍然难以捉摸。在此，证明了EZH 2在眼透镜中高度表达，并且AKT-EZH 2轴在TGFβ诱导的上皮-间质转化（EMT）中是重要的。更重要的是，已经确定MYPT 1/PP 1使EZH 2-S21去磷酸化，从而调节其功能。MYPT 1敲除加速EMT，但EZH 2-S21 A突变体的表达通过控制多个基因家族抑制EMT。此外，EZH 2的磷酸化状态和基因表达调节涉及人和小鼠眼睛中前囊下白内障（ASC）的控制。总之，结果鉴定了EZH 2-S21的特异性磷酸酶，并揭示了EZH 2去磷酸化控制涉及透镜EMT和ASC发病机制的几个基因家族。这些结果为EZH 2的功能和调控提供了重要的新信息。
The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2‐S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT‐EZH2 axis is important in TGFβ‐induced epithelial‐mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2‐S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2‐S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2‐S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.
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