经典Wnt信号负性调控TAZ表达的机制研究

项目名称： 经典Wnt信号负性调控TAZ表达的机制研究

项目编号： No.31501147

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 陈利华

作者单位： 温州医科大学

项目金额： 20万元

中文摘要： TAZ是哺乳动物细胞内Hippo信号的下游关键分子，Hippo 信号通过限制TAZ在细胞核内的累积并促进它的降解负性调控TAZ的功能。我们探索性的研究发现，在细胞非融合状态下，经典Wnt信号增加TAZ在丝氨酸89位的磷酸化，并下调细胞内TAZ的蛋白水平；而TAZ的siRNA显著地增加经典Wnt信号的活性，同时，免疫共沉淀发现细胞内TAZ和β-catenin、Lef1存在相互作用。因此本项目利用体外培养的细胞模型，进一步明确经典Wnt信号减少细胞内TAZ水平的分子机制，以及TAZ负性调控经典Wnt信号的分子机制。通过本项目的研究，将进一步丰富经典Wnt信号的调控机制，并揭开Hippo和经典Wnt信号之间新的cross-talk机制。

中文关键词： 经典wnt信号；TAZ；hippo通路；基因调控

英文摘要： TAZ functions as the downstream key factor of Hippo pathway in mammalian cell, Hippo pathway negatively regulates TAZ funciton by both limiting its nuclear accumulation and promoting its degradtion. Our premier study found that under cells were not completely contact,TAZ is down-regulated by canonical Wnt signaling, and is phosphorylated at serine 89 of TAZ, however, silence of TAZ expression significantly increases the activity of canonical Wnt signaling, and TAZ has interaction with Lef1 and β-catenin.We will further study the detailed mechanism by which canonical wnt signaling down-regulates TAZ levels, and by which TAZ negatively regulates canonical signaling in cells. This study will enrich the mechanism of canonical Wnt signalling, and will unveil a new cross-talk between Hippo and canonical Wnt signalling.

英文关键词： canonical wnt signaling;transcriptional coactivator with PDZ binding motif;hippo pathway;gene regulation