RanGTPase核质运输系统通过调控AIF核转移介导细胞凋亡的分子机制

项目名称： RanGTPase核质运输系统通过调控AIF核转移介导细胞凋亡的分子机制

项目编号： No.31501124

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： 梁海霞

作者单位： 太原理工大学

项目金额： 20万元

中文摘要： 凋亡诱导因子AIF可介导非caspase依赖的细胞凋亡途径，其促凋亡功能的发挥依赖于AIF核定位，但其转运入核的调控机制尚不明确。RanGTPase在细胞凋亡过程中调控多种凋亡相关蛋白的核质转运，同时Caspase信号通路可引起RanGTPase介导的核质运输机制受阻。前期研究发现，在无Caspase活性的模式生物嗜热四膜虫核凋亡中，RanGTPase参与AIF向凋亡细胞核转移的过程。本项目拟进一步分析RanGTPase核质运输系统参与人细胞凋亡初期AIF核输入过程及Importin介导的AIF入核分子机制，并探讨RanGTPase介导的AIF核输入与Caspase-3信号通路交互作用在细胞凋亡中的功能，最终揭示RanGTPase核质运输系统通过调控AIF核转移从而介导细胞凋亡的分子机制。研究结果有助于阐明AIF凋亡途径相关疾病的发病机制，并有望为促进细胞凋亡抗肿瘤药物提供新的治疗靶点。

中文关键词： 凋亡诱导因子；核转移；RanGTPase；细胞凋亡

英文摘要： The pro-apoptotic function of apoptosis-inducing factor (AIF), a caspase-independent apoptotic mediator, relies on nuclear translocation of AIF. However, the regulatory mechanism of the translocation of AIF to the nucleus of the apoptotic cells is undefined. During apoptosis, RanGTPase regulates nuclear-cytoplasmic transport of multiple apoptosis-associated proteins. And caspase-3 inactivates the RanGTPase-mediated nuclear transport machinery. Previously, we found that during the nuclear apoptosis of model organism Tetrahymena thermophila without caspase activity, RanGTPase is involved in the translocation of AIF to the apoptotic nucleus. This project will find out the involvement of RanGTPase nuclear-cytoplasmic transport system in nuclear import of AIF and the molecular mechanism of nuclear import of AIF directly mediated by Importin during apoptosis of human cells. And we will study the cross-talk between nuclear import of AIF regulated by RanGTPase and caspase-3 signal pathway, and its pro-apoptotic function. Finally, the study will reveal the molecular regulation of nuclear translocation of AIF-induced apoptosis by RanGTPase nuclear-cytoplasmic transport system. The results would be useful to clarify the pathogenesis of diseases related to AIF pathway-mediated cell apoptosis, and are expected to provide novel therapeutic targets for drugs inducing apoptosis of tumor cells.

英文关键词： AIF;nuclear translocation;RanGTPase;apoptosis