细胞周期激酶CDK16是CDK家族的新成员，在维持细胞生长、增殖、凋亡等生物学功能方面发挥着重要的调节作用，被认为是一个潜在的肿瘤癌蛋白，但其相互作用蛋白或底物分子目前尚未完全明确。申请人首次通过串联亲和纯化的方法发现CDK16可以与抑癌蛋白p53相互作用且负向调控其蛋白水平。进一步的预实验发现CDK16可能通过磷酸化p53的Serine315位点进而诱导其泛素化降解，提示p53可能是CDK16的一个新的底物分子。因此，本研究将进一步从分子水平探求p53被CDK16 磷酸化而促使其被泛素化降解，进而影响其稳定性，最终参与肺癌放疗抵抗的机制，同时明确CDK16 在肺癌中的临床表达及预后意义。本研究的完成对深入了解肺癌放疗抗拒分子机制有重要的理论意义，同时也可为肺癌治疗提供新的靶点。

Cyclin-dependent kinase CDK16, a new identified CDK family member, plays essential roles in diverse biological processes such as cell growth, proliferation, apoptosis and so on. Thus, it acts as a tumor onco-protein. However, the interacting proteins or substrates of CDK16 are largely unknown. Using tandem affinity purification method, our preliminary data show CDK16 binds to p53 and negatively controls the protein level of p53. In addition, CDK16 may be phosphorylate p53 at Serine315 site and then leads to the ubiquitination of p53. Therefore, this project intends to uncover: 1) CDK16 interacts with p53 both in vitro and in vivo; 2) CDK16 phosphorylates p53 and results in the ubiquitin-mediated degradation of p53; 3) The role of CDK16 in radioresistance of lung cancer; 4) The clinical significance and prognostic value of CDK16 in lung cancer. This study will demonstrate that how p53 is regulated by CDK16 mechanistically in lung cancer cells，and provide a novel molecular target for lung cancer.