LAUSR

SUMOylation plays important roles in diverse cellular processes by regulating protein-protein interaction, protein localization, trafficking, stability and activity. p53 can by SUMOyalted at lysine (K) 384. Yet, how SUMOylation regulates p53 activity remain unclear. SUMOylation can be revered by a group of proteins called deSUMOylating enyzme including the SUMO specific protease (SENP) family proteins. How p53 is regulated by deSUMOylation is also not well understood. Here, we show that SENP1 directly interacts with and desumoylates p53 in cells and in vitro. Depletion of SENP1 by siRNA-mediated knockdown drastically increased the p53 transactivation activity without inducing p53 protein levels, resulting p53-depndent cell cycle arrast. Further, SENP1 knockdown significantly promoted p53 transactivation activity in cells following DNA damage. Additionally, we found that SENP1 binds to and deSUMOylates PML and aborageted the enhancing effect of PML on p53 SUMOylation. Thus, SNEP1 is novel p53 desumoylating enzyme that regulates p53 activity but not its stability. Citation Format: Mushui Dai, Krishna Chauhan, Yingxiao Chen, Xiao-Xin Sun. SENP1 is a p53 deSUMOylating enzyme and its depletion induces p53 activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3536.