包括急性白血病在内的绝大多数肿瘤细胞通过激活端粒酶而弥补随细胞分裂逐渐缩短的端粒长度以获得永生。端粒长度受到多种蛋白质的调控，TRF1是第一个被发现的具有端粒长度负向调控作用的蛋白质，但其调控端粒长度的具体分子机制还有待于深入研究。本课题组在前期研究中发现了一个新的TRF1相互作用蛋白Aurora B，也证实了Aurora B在体外能够磷酸化修饰TRF1。本项目拟在前期工作基础上，鉴定TRF1的Aurora B磷酸化修饰位点，通过体内、体外磷酸化实验研究明确Aurora B激酶对TRF1的磷酸化修饰，观察Aurora B磷酸化修饰TRF1对TRF1功能及端粒长度的影响，并采用一系列细胞模型及动物实验进一步阐明Aurora B 磷酸化修饰TRF1在急性白血病发病过程中的作用及具体分子机制。研究结果将可能有助于进一步阐明急性白血病的发病机制，并有望发现新的急性白血病预后标志和治疗靶点。

In most human cancer cells which including leukemia cells, telomere length is maintained by the de novo addition of telomere repeats by telomerase. Some telomere-localizing proteins form a large complex termed the "shelterin/telosome",which is important for regulating telomeric structure and function. The first mammalian telomeric protein, now referred to as TRF1,was isolated based on its in vitro specificity for double-stranded TTAGGG repeats typical of vertebrate telomeres.TRF1 negatively regulates telomerase-dependent elongation, but how the TRF1 protein is involved in telomere length maintenance remains unclear. Our previous studies show that Aurora B is a novel TRF1-interacting protein.Aurora B can phosphorylate TRF1 in vivo and in vitro.In this study,we will try to further narrow down the phosphorylation site of TRF1 by Aurora B, and demonstrate the precise molecular mechanism and function of Aurora B-mediated phosphorylation in both TRF1 overexpression-induced apoptosis and its telomeric DNA regulating ability.This study will contribute to a better understanding of acute leukemia development mechanism and will provide new evidence that targeting TRF1 may be a promising therapeutic strategy for acute leukemia patients.