本文選題：YAP + YAP��； 參考：《遺傳》2017年07期

【摘要】：Hippo信號(hào)通路在個(gè)體發(fā)育與組織生長中發(fā)揮了關(guān)鍵的作用,YAP(Yes-associated protein)是該通路中主要的下游效應(yīng)因子。已有的研究表明YAP活性與腫瘤的發(fā)生發(fā)展密切相關(guān),然而關(guān)于YAP活性的調(diào)控機(jī)制目前還不是很清楚。本研究將YAP蛋白(NP_001123617)第425位蘇氨酸(T)突變?yōu)楸彼?A),發(fā)現(xiàn)YAP T425A突變能減弱YAP的轉(zhuǎn)錄活性,并通過免疫熒光實(shí)驗(yàn)發(fā)現(xiàn)該位點(diǎn)的突變還能阻滯YAP進(jìn)入細(xì)胞核。該位點(diǎn)對(duì)YAP活性的調(diào)控并不依賴于YAP在S127位點(diǎn)受到的磷酸化調(diào)控。同時(shí)本研究在細(xì)胞水平上檢測(cè)到T425A位點(diǎn)突變能部分降低YAP對(duì)細(xì)胞遷移的促進(jìn)作用。本研究主要揭示了YAP T425位點(diǎn)對(duì)YAP進(jìn)出細(xì)胞核及其轉(zhuǎn)錄活性調(diào)控的重要作用,豐富了Hippo通路的調(diào)節(jié)機(jī)理和YAP在腫瘤發(fā)生發(fā)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.
【作者單位】： 中國科學(xué)院大學(xué)生命科學(xué)學(xué)院;中國人民解放軍總醫(yī)院腫瘤科;中國科學(xué)院生物物理研究所腦與認(rèn)知國家重點(diǎn)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金項(xiàng)目(編號(hào):81402319) 北京市科技新星計(jì)劃項(xiàng)目(編號(hào):Z161100004916133)資助~~
【分類號(hào)】：R730.2

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本文編號(hào)：1995649