一个新的细胞周期调控基因fam72a的鉴定及其功能的研究

fam72a是一个功能未知的基因。虽然分子机制尚不明确，但既往研究表明fam72a的表达水平与细胞增殖呈正相关。我们在近期研究中发现，fam72a的表达受细胞周期调控，并在M期达到峰值。我们还发现，fam72a可以与调控细胞周期的重要磷酸酶PP2A结合，并促进PP2A招募特定的调节B亚基。fam72a与PP2A的结合影响了M期细胞内PP2A底物Hec1的磷酸化水平。据此，本项目提出如下研究假设:fam72a通过与蛋白磷酸酶PP2A相互作用调控有丝分裂活动相关蛋白的磷酸化水平，从而调控有丝分裂进程和细胞增殖。本课题旨在鉴定一个新的参与有丝分裂调控的成员fam72a，拟研究在fam72a调控下有丝分裂相关蛋白磷酸化水平的变化及其生物学效应，从而阐明fam72a基因的功能和作用机制。对fam72a功能的研究，将进一步丰富有丝分裂的调控机制，为研究细胞周期调控和肿瘤发生发展提供新的线索。

Fam72a is a newly identified gene of unknown function. Previous research has established that fam72a expression is positively correlated with cell proliferation in various cancer cells although the mechanism is unclear. We discovered that the expression of fam72a is regulated by cell cycle and peaks at M phase. We also found out that fam72a could bind to PP2A, an important phosphatase complex in cell cycle regulation. Upon binding, fam72a promotes PP2A recruiting specific regulatory B subunit. The interaction between fam72a and PP2A affects the phosphorylation of Hec1, a PP2A substrate in M phase. Accordingly, the following scientific hypothesis was proposed: fam72a changes the phosphorylation state of many cell cycle mediated proteins during mitosis through its interaction with PP2A and thereby regulates the progression of mitosis and cell proliferation. This project aims at identification of fam72a as a new member in cell cycle regulation. We seek to investigate the roles of fam72a in dephosphorylation of mitosis-related-proteins, evaluate the functional consequences of the phosphorylation state change and elucidate the molecular function of fam72a in mitosis. The result of this project will add a new piece in the jigsaw puzzle of the mitotic regulatory network and provide novel insight into cell cycle regulation and tumorigenesis.