乳腺癌是一种高度异质性常发病于女性的恶性肿瘤。在乳腺癌发生和发展进程中常伴随异常的乙酰化修饰。检查点抑制因子1（CHES1）作为一种转录因子被证实同多种类型癌症的发生发展存在密切的联系，申请者前期的研究发现CHES1具有抑制乳腺癌生长的功能，并首次在乳腺癌细胞中发现CHES1存在乙酰化修饰。这些结果暗示CHES1的乙酰化修饰可能在乳腺癌中发挥重要的调节作用。在此研究基础上，我们拟利用高分辨率质谱技术鉴定CHES1乙酰化修饰的位点，并构建乙酰化位点突变体，揭示乙酰化修饰对其蛋白稳定性、转录活性、亚细胞定位以及蛋白相互作用等方面的影响。并在细胞和小鼠模型中进一步探究CHES1的乙酰化修饰在乳腺癌的发生发展中发挥的分子调控机制。最后利用我们自主研发的高通量蛋白表达定量分析法，分析临床乳腺癌组织中CHES1的乙酰化水平，并探究其同乳腺癌的临床相关性，期望为乳腺癌的临床干预提供新的靶点和理论依据。

Breast cancer is one of heterogeneous malignancies in women worldwide. Acetylation is aberrantly active in the initiation and development of breast carcinoma. Mounting evidence confirmed that Checkpoint repressor 1 (CHES1), serves as a transcription factor, has a tight association with tumorigenesis and prognosis in many types of cancer. Our preliminary data firstly found that CHES1 repressed the tumorigenesis process of breast cancer and could be modified by acetylation, which indicated that CHES1 acetylation may play a crucial role in breast cancer, but the underlying mechanism of how acetylation regulate the CHES1 activity and further exhibit its regulatory role in development and progression of breast cancer needs to be elucidated. Therefore, this study is conducted to explore the effect of acetylation on the stability, transcriptional activity, subcellular location and protein interaction of CHES1 via identifying the acetylation sites and constructing the acetylation mutant plasmids of CHES1. Next, we aim to reveal the regulatory function of CHES1 acetylation on breast cancer progression in cell lines and mice model. Furthermore, we will also analyze the acetylation level of CHES1 in breast cancer tissue with our new high-throughput protein expression detection technology and uncovered the clinical relevance between CHES1 acetylation and breast cancer, it might provide new avenues for molecular-targeted therapy in breast cancer.