LAUSR

Nuclear factor erythroid-2 related factor 2 (NRF2) is a pivotal transcription factor; that maintains cellular redox homeostasis and facilitates the development of; malignant tumor phenotypes. At the molecular level, NRF2 promotes de novo serine; synthesis and SUMOylation affects its function. Our results indicated that the; SUMO1 acceptor site of NRF2 is the conserved lysine residue 110 (K110), and that; NRF2 SUMOylation deficiency inhibited tumorigenesis in hepatocellular carcinoma (HCC). Mechanistically, NRF2 SUMOylation promoted de novo serine synthesis in HCC by enhancing the clearance of intracellular reactive oxygen species (ROS) and up-regulating phosphoglycerate dehydrogenase (PHGDH). More importantly, serine; starvation increased the level of NRF2 SUMOylation, leading to sustained HCC; growth. Collectively, our results indicate the presence of a novel NRF2; SUMOylation-mediated signaling process that maintains HCC tumorigenesis in; normal conditions and in response to metabolic stress.