PARP10是第一个被鉴定的单ADP核糖转移酶，在DNA损伤修复和信号转导中有重要功能。我们最近发现PARP10是肿瘤转移抑制基因，其通过单ADP核糖修饰Aurora A并抑制其激酶活性来抑制肿瘤转移（Oncogene，2018）。在该课题的研究中，我们发现RNF114与PARP10相互作用，并通过K27和K33连接方式泛素化PARP10，但不影响其蛋白稳定性；RNF114缺陷显著降低PARP10及其底物Aurora A的ADP核糖修饰水平，从而增强Aurora A激酶活性和底物AKT的磷酸化水平，导致肝癌细胞迁移和侵袭能力增强。本课题将在此基础上，分析RNF114表达水平与肝癌患者生存预后的关系并揭示RNF114在肝癌转移中的功能；鉴定PARP10泛素化位点并探讨其对PARP10功能的影响，最终阐明RNF114通过泛素化PARP10抑制肝癌转移的分子机制，为肝癌诊疗提供新的分子靶标。

PARP10 is the first identified mono-ADP-ribosyltransferase and plays an important role in DNA damage response and signal transduction. Recently, we have demonstrated that PARP10 is a tumor metastasis suppressor（Oncogene，2018）. We found that PARP10 mono-ADP-ribosylated Aurora A and inhibited its kinase activity, then negatively regulated tumor metastasis. During this project, we also found that RNF114 is a new partner of PARP10. RNF114 ubiquitinated PARP10 through K27 and K33, although did not affect its stability. RNF114 deficiency dramatically decreased the mono-ADP-ribosylation level of PARP10 and its substrate Aurora A, and then increased the kinase activity of Aurora A and the phosphorylation of its substrate AKT, leading to dramatically increase the migration and invasion of hepatocellular carcinoma cells. In this study, we will analyze the relationship between the expression level of RNF114 and the survival prognosis of patients with hepatocellular carcinoma, and reveal the function of RNF114 in hepatocellular carcinoma metastasis. We will further identify the ubiquitination site of PARP10 and investigate its effect on PARP10’s function. Finally, we will elucidate the molecular mechanism of RNF114 inhibiting hepatocellular carcinoma metastasis through ubiquitination of PARP10, and provide new molecular targets for the diagnosis and treatment of hepatocellular carcinoma.