Roles of CtBP in cancer and its mechanism of action

描述（由申请人提供）： 该建议涉及CtBP的作用及其在癌症中的作用机制。CtBP是一种重要的辅阻遏物，参与胚胎发育、细胞分化和肿瘤发生。然而，对其作用机制知之甚少。我已经成功地纯化了CtBP复合物。在本申请中，我建议1）使用我的同事和我最近开发的基于DNA载体的RNAi技术来研究CtBP复合物的不同组分在CtBP介导的阻遏中的功能作用。本研究将以E-cadherin基因为模型，分析这些组分对E-cadherin基因失活的贡献及其对肿瘤发生的影响。2)使用染色质免疫沉淀（CHIP）分析确定与CtBP相关的E-钙粘蛋白启动子的局部染色质变化，以提供将染色质重塑与CtBP介导的抑制联系起来的分子证据。3)表征CtBP复合物中的新锌指蛋白ZNF 217，以揭示其在乳腺癌中隐含作用的分子基础。

DESCRIPTION (provided by applicant): This proposal deals with the roles of CtBP and its mechanism of action in cancer. CtBP is a crucial co-repressor involved in embryonic development, cell differentiation and tumorigenesis. However, little is known about its mechanism of action. I have succeeded in the purification of the CtBP complex. In this application, I propose to 1) Study functional roles of different components of CtBP complex in the CtBP mediated repression using the DNA vector-based RNAi technology which was developed recently by my co-workers and myself. I will use the E-cadherin gene as a model to analyze the contributions of these components to the inactivation of E-cadherin gene and the effects on tumorigenesis. 2) Identify local chromatin changes at the E-cadherin promoter that are associated with CtBP using chromatin immunoprecipitation (CHIP) assays to provide molecular evidence linking chromatin remodeling to CtBP-mediated repression. 3) Characterize a new zinc finger protein ZNF217 in the CtBP complex to reveal the molecular basis for its implied role in breast cancers.