遗传 ›› 2017, Vol. 39 ›› Issue (7): 675-682.doi: 10.16288/j.yczz.17-068

• 研究报告 • 上一篇    

YAP蛋白T425A位点突变对YAP功能的影响

杨阳露1(),邹壮志1,袁方2(),毛蓓蓓3()   

  1. 1. 中国科学院大学生命科学学院,北京 100049
    2. 中国人民解放军总医院肿瘤科,北京 100853
    3. 中国科学院生物物理研究所,脑与认知国家重点实验室,北京 100101
  • 收稿日期:2017-02-28 修回日期:2017-04-18 出版日期:2017-07-20 发布日期:2017-07-04
  • 作者简介:杨阳露,硕士研究生,专业方向：分子生物学。E-mail: luyaoyao0@163.com|袁方,博士,副主任医师,研究方向：肿瘤学。E-mail: yuanfsc@gmail.com|毛蓓蓓,博士,副研究员,研究方向：肿瘤分子生物学。E-mail: m8244@163.com
  • 基金资助:
    国家自然科学基金项目(81402319);北京市科技新星计划项目(Z161100004916133)

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

lu Yang1(),Zhuangzhi Zou1, 2(),Beibei Mao3(),   

  1. 1. College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
    2. Department of Oncology, Chinese PLA General Hospital, Beijing 100853, China
    3. State key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • Received:2017-02-28 Revised:2017-04-18 Online:2017-07-20 Published:2017-07-04
  • Supported by:
    the National Natural Science Foundation of China(81402319);Beijing Novel Project(Z161100004916133)

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摘要：

Hippo信号通路在个体发育与组织生长中发挥了关键的作用,YAP(Yes-associated protein)是该通路中主要的下游效应因子。已有的研究表明YAP活性与肿瘤的发生发展密切相关,然而关于YAP活性的调控机制目前还不是很清楚。本研究将YAP蛋白(NP_001123617)第425位苏氨酸(T)突变为丙氨酸(A),发现YAP T425A突变能减弱YAP的转录活性,并通过免疫荧光实验发现该位点的突变还能阻滞YAP进入细胞核。该位点对YAP活性的调控并不依赖于YAP在S127位点受到的磷酸化调控。同时本研究在细胞水平上检测到T425A位点突变能部分降低YAP对细胞迁移的促进作用。本研究主要揭示了YAP T425位点对YAP进出细胞核及其转录活性调控的重要作用,丰富了Hippo通路的调节机理和YAP在肿瘤发生发展中的作用研究。

关键词: YAP, YAP T425A, YAP转录活性, YAP核定位, 细胞迁移

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.

Key words: YAP, YAP T425A, YAP transcriptional activity, YAP nuclear localization, cell migration