Journal
CANCER LETTERS
Volume 466, Issue -, Pages 39-48Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.09.010
Keywords
Nuclear factor erythroid-2 related factor 2; Small ubiquitin-like protein; Serine synthesis; Hepatocellular carcinoma; Reactive oxygen species
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Funding
- Natural Science Foundation of China [81572691, 81872230]
- National Basic Research Program of China [2015CB910400]
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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.
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