控制细胞分裂所必需的调控因子是抑制癌细胞恶性增殖的常用策略。作为调节有丝分裂的关键蛋白激酶，Plk1在许多肿瘤组织中过量表达，因而成为抗癌的重要靶标和细胞周期研究的重要课题。我们的预实验初步鉴定了Plk1新的结合蛋白PIP。我们将深入分析Plk1结合PIP的分子基础，探究两者的结合在细胞周期中的时空动态变化规律，全面分析Plk1与PIP的相互作用在调控细胞周期的G2/M期转换、有丝分裂期染色体整列等方面的重要功能。我们推测，PIP通过分别结合蛋白激酶Aurora A和Plk1促成Plk1第210位苏氨酸的磷酸化，进而激发并维持Plk1的活性，确保有丝分裂的正常进行。我们将验证这一假设，并探讨PIP与Plk1的其他结合蛋白一起协同调控Plk1的分子机制。本项目的顺利实施，将揭示调控有丝分裂进程和染色体分离的新机制，丰富相关基础理论，并为有丝分裂蛋白激酶靶向的抗癌研究提供新的依据。

An important hallmark of tumor cells is the uncontrolled proliferation and cell division. Inhibiting the activity of essential mitotic regulatory factors is a usual strategy to limit the malignant proliferation of cancer cells. As the key regulator of mitosis, the protein kinase, Plk1 is over-expressed in many kinds of tumors, and therefore becomes a promising target for the cancer therapeutics. Understanding how Plk1 activity is regulated in mitosis is an important research topic. In our preliminary experiments, we have identified a new Plk1-interacting protein (PIP). In this study, we aim to reveal the molecular basis for the PIP-Plk1 interaction. We will examine the spatio-temporal dynamic interaction of PIP with Plk1 in the cell cycle. We will design a series of experiments to determine the important roles of the PIP-Plk1 interaction in the regulation of timely G2/M transition and normal chromosome alignment in mitosis. We speculate that PIP interacts with protein kinases Aurora A and Plk1, which promotes the phosphorylation of Plk1 at threonine 210, thereby triggering and maintaining Plk1 activity to guarantee the normal mitotic progression. We will also examine how PIP cooperates with other known Plk1-binding proteins to regulate Plk1 in mitosis. Upon successful conclusion of this study, we will have revealed new mechanisms for the regulation of mitosis progression and chromosome segregation, which will also help the development of anti-mitotic cancer therapy.