E2泛素交联酶RAD6的核转位机制研究

项目名称： E2泛素交联酶RAD6的核转位机制研究

项目编号： No.31201051

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： 陈苏

作者单位： 同济大学

项目金额： 23万元

中文摘要： DNA损伤修复及染色质结构与基因表达的调节在肿瘤的发生和发展过程中发挥着重要的作用。研究发现，E2泛素交联酶RAD6广泛地参与到上述重要的生物学过程中。RAD6通过泛素化PCNA成为调控DNA损伤修复途径的枢纽蛋白；通过对组蛋白H2B泛素化以及H3甲基化的调节显著地影响染色质结构和基因表达；RAD6的表达水平及其核转位与肿瘤的发生和恶性程度密切相关。此外，我们的研究还发现，RAD6在维持体内适当的p53蛋白水平方面也起着至关重要的调控作用。RAD6的诸多生物学功能与细胞核密切相关，它的正确核定位对其功能的执行至关重要。而RAD6蛋白本身不存在核定位信号，因此，了解RAD6的核转位机制对全面理解RAD6的功能调控十分必要。本项目通过寻找调控RAD6核转位的相互作用蛋白，阐明其调控的分子机理。然后，以RAD6的核转位为切入点，详细分析RAD6的核转位及其调控蛋在肿瘤发生和发展中的作用机制。

中文关键词： RAD6；核转位；磷酸化；CDK1；

英文摘要： DNA damage repair and the regulation of chromatin structure and gene expression play important roles in carcinogenesis and cancer development. It was reported that RAD6 participates in these biological processes thoroughly. RAD6 is a node protein in directing different DNA damage repair pathways by differential ubiquitination of PCNA; RAD6 affects chromatin structure and gene expression via the regulation of H2B monoubiquitination and H3 methylation. The protein level and nuclear translocation of RAD6 is highly correlated to carcinogenesis and metastasis. Besides, our published data showed that RAD6 also plays critical role in controlling p53 in an appropriate protein level. Most of the functions of RAD6 are significantly related to the nucleus. Therefore, the precise nuclear translocation of RAD6 is critical to its normal biological function. However, RAD6 has no nuclear localization signal (NLS). Thus, it is ensential to investigate the mechanisms of RAD6's nuclear translocation in understanding the functional regualtion of RAD6. We will focus on the dissection of the molecular mechamisms of RAD6's nuclear translocation, find the interacting proteins regulating the nuclear translocation of RAD6 and elucidate the regulational mechanisms of these interactions, then further analysis the effects of this translocat

英文关键词： RAD6；Nuclear Translocation；Phosphorylation；CDK1；