锌指蛋白ZER6属于Cys2His2 like（C2H2）型锌指蛋白，在肿瘤细胞中呈异常表达，然而有关它在生物功能中的作用机制报道极少。细胞周期调控机制紊乱是导致肿瘤细胞无限增殖的根本原因。课题组前期应用shRNA表达质粒文库对影响细胞周期抑制因子p21转录活性的因子进行高通量筛选，发现敲减锌指蛋白ZER6显著促进p21转录活性，然而，ZER6调控细胞周期的详细分子机制尚待深入探讨。本课题拟从以下三方面展开研究：（1）揭示锌指蛋白ZER6对p21的作用机制及其对细胞周期调控的影响；（2）阐明肿瘤抑制因子p53在ZER6/p21信号通路中的作用机制；（3）解析ZER6/p21信号通路在细胞周期及其相关的细胞增殖及凋亡中的作用。通过本项目研究将揭示锌指蛋白ZER6/p21信号通路在细胞周期调控中的分子机制，为细胞周期调控提供新的理论基础，也为肿瘤等细胞周期紊乱相关疾病的诊治提供生物学新靶标。

Zinc finger protein ZER6 is a member of Cys2His2 like (C2H2) zinc finger protein family. ZER6 displays aberrantly low expression level in tumor lesions; however, its biological function is poorly characterized. Cell cycle is a tightly controlled fundamental process in living cells, and is closely related to other biological functions, including cell proliferation and apoptosis. Cell cycle progresses in a directional manner following well-ordered events, and defects in cell cycle regulation are closely linked to various abnormalities, such as unlimited cell proliferation that leads to cancer. Despite of its critical function, cell cycle control mechanism remains as a basic scientific problem that has not been totally elucidated. In our previous experiment, we have performed a screening for determining factors that could regulate the transcriptional activity of p21, a master regulator of cell cycle, by using a short hairpin RNA (shRNA) expression vector library. Through this screening, we found that knocking down ZER6 significantly increased p21 transcriptional activity; however, the detail mechanism of ZER6 regulation on cell cycle progression remains to be elucidated. Accordingly, in this study, we will unravel the novel role of ZER6 in cell cycle regulation. To this end, we will perform investigations as below: (1) we will elucidate the role and molecular mechanism of ZER6 in regulating p21 and cell cycle; (2) we will unravel the function of tumor suppressor gene p53, which is an upstream transcriptional regulator of p21, in regulating ZER6/p21 pathway; (3) we will elucidate the roles of ZER6/p21 pathways in tumor cells proliferation and apoptosis, and subsequently, in tumorigenesis. This study will not only uncover novel biological roles of ZER6, especially in cell cycle regulation, but also will provide new insights regarding the molecular mechanisms of cell cycle. Subsequently, our study will also give new perspective regarding the potential of using ZER6 as a marker for diseases related to cell cycle defect, as well as its potential as novel molecular target for treating them.