p53异构体泛素化的调节机制

项目名称： p53异构体泛素化的调节机制

项目编号： No.31201057

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 刘赓

作者单位： 苏州大学

项目金额： 23万元

中文摘要： 泛素化广泛参与细胞内各项生理活动。p53作为最重要的抑癌因子之一，其蛋白稳定性和活性受到泛素化的严格调控。随着p53异构体的被发现，它们在肿瘤产生中的作用也在慢慢被揭示，而对它们自身调控的研究却几乎是空白。因此，本课题通过对p53异构体泛素化的研究，找出参与泛素化的因子，探索它们自身稳定性及活性调节的机制，进一步了解它们和野生型p53的相互调控和影响。同时，为研究开发异构体泛素化调节剂提供理论依据，最终达到提高肿瘤放射治疗增敏的效果。

中文关键词： p53β；诱导表达；泛素化；；

英文摘要： Ubiquitination is involved in essentially all of the intracellular processes in eukaryotes. As one of the most important tumour suppressors, p53 stability and activity is tightly regulated by its ubiquitination. The discovery of various p53 isoforms reveals more complicated mechanisms of how p53 suppresses tumours. However, the regulation of p53 isoforms has been properly studies. Thus, this project aims to investigate the ubiquitination of p53 isoforms, and discover the enzymes involved. Moreover, the impact of ubiquitination on the stability and activity of the p53 isoforms will be analysed. The effects of ubiquitination of p53 isoforms in regulating wild-type p53 functions will also be inspected. Finally, this study will provide useful information on the development of inhibitors/enhancers targeting the pathway of p53 isforms ubiquitination. Eventually the application of the inhibitors/enhancers will increase the sensitivity of tumours in response to radiotherapy.

英文关键词： p53β；inducible system；ubiquitination；；