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YAP T425A突变在YAP活性调控中的作用。

The roles of YAP T425A mutation in the regulation of YAP activity.

作者信息

Yang Yang-lu, Zou Zhuang-zhi, Fang Yuan, Mao Beibei

机构信息

College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Department of Oncology, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Yi Chuan. 2017 Jul 20;39(7):675-682. doi: 10.16288/j.yczz.17-068.

DOI:10.16288/j.yczz.17-068
PMID:28757481
Abstract

The Hippo signaling pathway plays a critical role in body development and tissue growth. As the core effector of the Hippo signaling pathway, Yes-associated protein (YAP) has been reported to be involved in various kinds of human cancers. However, the mechanism for the regulation of YAP activity has not been completely understood. In this study, we constructed a YAP Thr425Ala mutant and found that this mutation decreased YAP transcriptional activity. Further, T425A retained YAP in the cytoplasm without affecting the phosphorylation of YAP S127. Moreover, we observed that the T425A mutation attenuated the ability of YAP in driving MCF10A cell migration. Our research indicates that T425 of YAP is important for the regulation of YAP localization and activity.

摘要

河马信号通路在机体发育和组织生长中发挥着关键作用。作为河马信号通路的核心效应器,Yes相关蛋白(YAP)已被报道参与多种人类癌症。然而,YAP活性调控的机制尚未完全明确。在本研究中,我们构建了YAP Thr425Ala突变体,发现该突变降低了YAP的转录活性。此外,T425A使YAP保留在细胞质中,而不影响YAP S127的磷酸化。而且,我们观察到T425A突变减弱了YAP驱动MCF10A细胞迁移的能力。我们的研究表明,YAP的T425对于YAP定位和活性的调控很重要。

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