YAP蛋白T425A位点突变对YAP功能的影响

发布时间：2018-06-08 11:33

本文选题：YAP + YAP　；参考：《遗传》2017年07期

【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。
[Abstract]:Hippo signaling pathway plays a key role in ontogenesis and tissue growth. YAPP Yes-associated protein is the main downstream factor in this pathway. Previous studies have shown that YAP activity is closely related to tumorigenesis and development, but the mechanism of YAP activity regulation is not clear. In this study, the mutation of YAP protein NPS (NPD 001123617) was transformed into Ala. It was found that YAP T425A could attenuate the transcriptional activity of YAP, and the mutation at this site could block the entry of YAP into the nucleus by immunofluorescence assay. The regulation of YAP activity does not depend on the phosphorylation of YAP at S127 site. At the same time, we found that T425A mutation could partially reduce the effect of YAP on cell migration. This study mainly revealed the important role of YAP T425 site in regulating the nuclear entry and exit of YAP and its transcriptional activity, which enriched the regulation mechanism of Hippo pathway and the role of YAP in tumorigenesis and development.
【作者单位】：中国科学院大学生命科学学院;中国人民解放军总医院肿瘤科;中国科学院生物物理研究所脑与认知国家重点实验室;
【基金】：国家自然科学基金项目(编号:81402319) 北京市科技新星计划项目(编号:Z161100004916133)资助~~
【分类号】：R730.2

【相似文献】