翻译后修饰异常是肿瘤中除突变外导致p53失活或转变的关键分子事件。我们前期在国际胶质母细胞瘤（GBM）数据库和组织芯片中发现p53在RNA和蛋白水平显著增高，且乙酰化p53阳性者显示有较好生存预期，但近半p53阳性者显示乙酰化p53阴性。预实验发现这与GBM中高表达的Smad1抑制p53磷酸化并促使乙酰转移酶p300优先促进STAT3乙酰化有关，而E3连接蛋白TRIM21调控了Smad1的核-浆转运，因此提出Smad1/TRIM21-p300-p53/STAT3选择性乙酰化假说：GBM中Smad1与TRIM21结合促进Smad1泛素化和核聚集，进而抑制p53磷酸化导致与p300亲和力降低，Smad1招募p300和STAT3组成乙酰化调节复合体促进STAT3乙酰化和活性。本课题将通过体内、外多层次研究进一步明确该假说，揭示其功能及机制，为胶质母细胞瘤的防治提供新靶点和新思路。

Post-translational modification aberrant is a key molecular event which causes p53 tumor suppressor function loss or transformation in tumors except mutation. Our previous data showed that p53 in RNA and protein level is significantly increased in Glioblastoma (GBM) tissues; p53 acetylation predicted better survival outcomes, while nearly half of p53 positive cases showed acetylation p53 negative. Here, we found that it’s associated with the overexpression of Smad1 in GBM. Smad1 inhibits p53 phosphorylation and promotes STAT3 acetylation by acetyl transferase p300. E3 ubiquitin-protein ligase，TRIM21 regulates nuclear–cytoplasmic shuttling of Smad1. Thus, we proposed a Smad1/TRIM21-p300-p53/ STAT3 selective acetylation mechanism in GBM: TRIM21 binds Smad1 and promotes Smad1 ubiquitin and nucleus aggregation, then inhibits p53 phosphorylation resulting in lower affinity with p300; Smad1 recruits p300 and STAT3 to compose an acetylation-regulating complex and promotes STAT3 acetylation. This study will further clarify the hypothesis through in vivo and in vitro experiments, reveal its function and mechanism, and provide potential targets and new ideas for the prevention and treatment of glioblastoma.