Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 168, Issue -, Pages 129-141Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.03.034
Keywords
NRF2; Regulation; Cellular protection; Oxidative stress; Phosphorylation; Posttranslational modification
Funding
- National Natural Science Foundation of China [81930100, 81773581, 81773639]
- Double First Class Innovation Team of China Pharmaceutical University [CPU2018GY02]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZ202003]
- Program for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education
- Young Elite Scientists Sponsorship Program by CAST [YESS20180146]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Qing Lan Project of Jiangsu Province
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NRF2 is involved in antioxidant pathways and physiological processes, dysregulation is linked to diseases, phosphorylation by kinases is critical in regulating NRF2 activity. Various kinases positively or negatively regulate NRF2 activity through phosphorylation of different sites.
The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.
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