CDK11 safeguards the identity of human embryonicstem cells via fine-tuning signaling pathways

Jianyi Ding; Zhuoqing Fang; Xinyuan LiuZhexin ZhuChunsheng WenHan WangJunjie GuQing-run LiRong ZengHui LiYing Jin

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CDK11 safeguards the identity of human embryonicstem cells via fine-tuning signaling pathways

机译：CDK11保障人类的身份embryonicstem细胞通过微调信号通路

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Signaling pathways transmit extracellular cues into cells and regulate transcriptome and epigenome to maintain or change the cell identity. Protein kinases and phosphatases are critical for signaling transduction and regulation. Here, we report that CDK11, a member of the CDK family, is required for the maintenance of human embryonic stem cell (hESC) self-renewal. Our results show that, among the three main isoforms of CDK11, CDK11~(p46) is the main isoform safeguarding the hESC identity. Mechanistically, CDK11 constrains two important mitogen-activated protein kinase (MAPK) signaling pathways (JNK and p38 signaling) through modulating the activity of protein phosphatase 1. Furthermore, CDK11 knockdown activates transforming growth factor (3 (TGF-β)/SMAD2/3 signaling and upregulates certain nonneural differentiation-associated genes. Taken together, this study uncovers a kinase required for hESC self-renewal through fine-tuning MAPK and TGF-β signaling at appropriate levels. The kinase-phosphatase axis reported here may shed new light on the molecular mechanism sustaining the identity of hESCs.

机译：细胞外信号通路传输信号进细胞,调节转录组和表观基因组保持或改变细胞的身份。信号转导和的关键监管。CDK家庭的需要维护人类胚胎干细胞(hESC)自我更新。三个主要的亚型CDK11, CDK11 ~ (p46)是主要同种型维护hESC身份。从力学上看,CDK11约束两个重要增殖蛋白激酶(MAPK)信号通路(物和p38信号)调节蛋白磷酸酶1的活性。此外,CDK11击倒激活转化生长因子(3 (TGF -β)/ SMAD2/3信号和某些nonneural上调differentiation-associated基因。本研究揭示了一个激酶hESC所必需的自我更新通过微调MAPK和TGF -β信号在适当的水平。kinase-phosphatase轴报道这里可能会脱落新的分子机制维持为的身份。

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《Journal of cellular physiology.》 |2020年第5期|4279-4290|共12页
作者
Jianyi Ding; Zhuoqing Fang; Xinyuan LiuZhexin ZhuChunsheng WenHan WangJunjie GuQing-run LiRong ZengHui LiYing Jin;
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CAS Key Laboratory of Tissue Microenvironment and Tumor, Chinese Academy of Sciences, Shanghai;

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正文语种英语
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关键词
PITSLRE Serine/Threonine-Protein Kinase CDC2L1; Phosphoprotein Phosphatases; Human Embryonic Stem CellsTGF-beta Signaling Pathway KEGGMAPK Signaling PathwaySignal Transduction;

机译：PITSLRE丝氨酸/ Threonine-Protein激酶CDC2L1;磷蛋白磷酸酶;人类胚胎干细胞CellsTGF-beta信号通路PathwaySignal KEGGMAPK信号转导;

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CDK11 safeguards the identity of human embryonicstem cells via fine-tuning signaling pathways

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