Plk1 是一种在细胞周期调控中起关键作用的蛋白激酶，近年来有研究提示Plk1参与端粒复制的调控，但分子机制尚不明确。我们前期研究发现Plk1可以结合端粒酶催化亚基hTERT, 初步结果显示hTERT能被Plk1磷酸化。为了阐明Plk1调控端粒酶活性的分子机制，我们拟进行以下几个方面的研究：（1）确定Plk1对端粒酶hTERT的磷酸化位点；（2）分析PLK1对hTERT磷酸化修饰是否影响端粒酶活性和端粒复制；同时研究Plk1是否影响hTERT与端粒酶RNA（hTR）的结合以及hTERT在细胞内定位和稳定性；（3）通过分析临床样本和小鼠成瘤模型，明确Plk1表达水平与hTERT活性的相关性，并了解hTERT磷酸化修饰在肿瘤发生发展中的作用。通过上述研究揭示Plk1调节端粒酶活性及端粒复制的机理，为探索Plk1协同hTERT在调控细胞增殖及肿瘤发生发展中的作用提供思路和基础。

The Plk1 (Polo-like-kinase 1) is a Ser/Thr protein kinase, which is increasingly recognized as key regulators during cell division through phosphorylation of different substrates. It regulates G2/M transition, spindle formation, chromosome segregation and process of cytokinesis. Recent research has prompted that the Plk1 is also involved in telomere replication, but the molecular mechanism is not clear. Our preliminary data indicated that Plk1 can interact with telomerase catalytic subunit hTERT. We also identified the binding region of hTERT with Plk1. More importantly, we found that Plk1 can phosphorylate hTERT. In order to investigate the molecular mechanism of Plk1 in regulating the replication of telomere and the activity of hTERT, we propose to accomplish the following specific aims: (1) To identify the phosphorylation site(s) of hTERT by Plk1, and analyze whether its phosphorylation affects its telomerase activity; (2) To analyze whether Plk1 regulates the association of hTERT with hTR and the subcellular localization of hTERT as well as its stability ; (3) To study the correlation of the activity of Plk1 and hTERT during different phases of cell cycle and reveal the relevance of Plk1 and hTERT with cell proliferation and tumorigenesis.