HMGA2、p53均是与结肠癌发生发展密切相关的重要原癌蛋白，但它们的关系尚不明确。我们前期研究高度提示HMGA2与p53、MDM2之间可以直接结合，并利用正反向Co-IP实验进行了验证，进一步通过截断蛋白Co-IP实验明确了它们的结合位点。我们在前期构建的肠道特异性Hmga2 KI小鼠成瘤模型中发现Hmga2能显著促进肠道肿瘤形成。本项目拟在此基础上，通过全长及截短Co-IP、GST pull-down、酵母双杂交、p53泛素化、CHX、MG132处理等实验，揭示HMGA2通过MDM2依赖的途径促进p53泛素化降解的过程及分子机制，阐明HMGA2通过p53依赖的途径调控细胞周期和凋亡，并利用多种基因修饰小鼠揭示Hmga2及p53相互作用对结肠癌发生发展的影响，进而完成HMGA2与p53蛋白之间的交互作用关系及分子机制的系统深入研究，为今后以此为靶点进行临床干预提供实验基础和理论依据。

HMGA2 and p53 are both oncoproteins that are involved in colorectal (CRC) carcinogenesis. However, their relationship is still unclear. Our previous studies indicated that HMGA2 bound directly to p53 and MDM2, which were verified by Co-IP assay. Furthermore, the exact binding sites were determined. On the basis of the Hmga2 knock-in mice lines, which conditionally expressed Hmga2 in the intestine, we found that Hmga2 was able to promote the intestinal tumorigenesis. In this study, we hypothesize that HMGA2-mediated p53 ubiquitination plays an important role in tumorigenesis and tumor progression of colorectal cancer, in a MDM2 dependent way. Co-IP, GST pull-down, yeast two-hybrid, ubiquitination assays and genetically modified mice were applied. Taken together, our study provides new insights into the mechanisms of HMGA2’s role in colorectal cancer and new therapeutic targets for the treatment of CRC cancer.