Role of p53-citrullination in human carcinogenesis

在这个项目中，我们在体内和体外通过p53-PADI4途径鉴定了组蛋白H4的精氨酸3残基（cit-H4R3）的瓜氨酸化对DNA损伤的响应。我们还发现DNA损伤诱导的Lamin C.瓜氨酸化Padi4（-/-）小鼠胸腺对辐射诱导的细胞凋亡表现出抗性。我们还发现在癌症组织和细胞系中经常发生功能突变丧失。我们的发现揭示了PADI4作为肿瘤抑制基因的可能作用。

In this project, we have identified in vivo and in vitro citrullination of the arginine 3 residue of histone H4 (cit-H4R3) in response to DNA damage through the p53-PADI4 pathway. We also show DNA damage-induced citrullination of Lamin C. Padi4(-/-) mice exhibit resistance to radiation-induced apoptosis in the thymus. We also found frequent loss of function mutations in cancer tissues and cell lines. Our findings reveal the possible role of PADI4 as a tumor suppressor gene.