诱导细胞分化是治疗白血病的有效途径，而治疗靶点或信号通路的确定是逆转异常分化的关键。本课题组在筛选白血病分化关联基因的基础上，首次发现肽基精氨酸脱亚胺酶4（PADI4）与白血病细胞分化密切相关，同时证实PADI4可以调控sox4表达，并能通过相互作用介导sox4瓜氨酸化。而文献报道sox4是一个重要的白血病细胞分化调节因子。因此，我们推测PADI4对sox4的靶向调控及瓜氨酸化修饰可能是PADI4调控白血病细胞定向分化的关键机制。本项目拟在前期研究基础上，深入分析PADI4在白血病细胞分化过程的功能，并进一步从PADI4对sox4表达调控、功能调控及二者是否协同调控白血病细胞分化三个方面展开相关机制研究。旨在阐明PADI4在白血病细胞分化过程中的功能及关键机制，为将PADI4作为白血病治疗靶点提供理论依据和实验线索。

Inducing differentiation of leukemic cells is an effective way to treat leukemia. The key issue to reverse the abnormal differentiation is to select appropriate therapeutic targets or signaling pathway. On the basis of screening leukemia differentiation related gene, we first discovered peptidylarginine deiminase 4 (PADI4) is closely associated with the differentiation of leukemia cells. Furthermore, we also confirmed that PADI4 could regulate the expression of sox4, and modify it as well through citrullination. Based on the reports that SOX4 is an important regulator of the differentiation of leukemia cells, we hypothesized that the regulatory effects of PADI4 exerted on sox4 may be the key mechanism which accounted for the function that PADI4 regulating differentiation of leukemia cell. In this project, we plan to study the function of PADI4 in the differentiation of leukemia cell lines. Further study regarding the molecular mechanism of PADI4 would also be lauched in leukemia cells as following: (1) how does PADI4 regulate sox4 expression;(2)the effects of PADI4 on the function of sox4;(3)whether or not PADI4 coordinate sox4 during differentiation process. Above all, our progect aim to elucidate the function and the key mechanism of PADI4 during the differentiation of leukemia cell lines, which also make PADI4 as interference target feasible and applicabe.