PTEN是重要的抑癌基因，在维护基因组稳定性方面具有重要作用。基因组不稳定是癌症发生的重要条件。研究显示，PTEN很可能通过不同的翻译后修饰，参与多重机制，防止基因组不稳定的发生。最近，我们鉴定出了PTEN SUMO化的新位点，并证实其参与预防DNA双链断裂（DSBs）。另一方面，我们发现了PTEN的新激酶STK38及其所催化的磷酸化位点，该激酶很可能通过磷酸化PTEN调控有丝分裂检验点。本项目将探讨PTEN SUMO化及磷酸化的调控机制，阐述其如何参与DNA损伤预防及有丝分裂检验点激活，并进一步探讨PTEN SUMO化及磷酸化两种修饰之间的协同作用，深入阐明PTEN如何通过翻译后修饰参与不同通路的调节，以维护基因组稳定性。我们近期建立了与PTEN SUMO化、磷酸化相关的系列基因敲入小鼠模型，本项目将利用这些模型，结合肿瘤样本分析，综合评价PTEN翻译后修饰在抑制肿瘤发生发展中的作用。

Genome instability is the most significant hallmark of cancer. It is crucial, if not indispensable, for cancer initiation. Tumor suppressor PTEN plays an very important role in guarding the genome. PTEN may participate in multiple mechanisms to maintain genome stability. Recently, we identified new SUMOylated site on PTEN and demonstrated that the modified PTEN prevents DNA double-strand breaks (DSBs). On the other hand, we found a new kinase, STK38, associated with PTEN and catalyze PTEN phosphorylation. STK38 may activate the mitotic checkpoint through phosphorylating PTEN. In this project, we will study the regulation of PTEN SUMOylation and phosphorylation and how these modifications participate in DNA damage prevention and mitotic checkpoint activation. We will further test if these two modifications of PTEN maintain genome stability in cross-talk manner or in parallel way. We will use the established mouse models, which is related to the modifications mentioned above, and patient samples analysis to evaluate the role of PTEN modifications in tumor suppression.