MAPK15 controls cellular responses to oxidative stress by regulating NRF2 activity and expression of its downstream target genes

• DOI: 10.1016/j.redox.2024.103131
• Publication Date: 2024-03-28T15:32:05Z
• Authors: Lorenzo Franci; Giulia Vallini; Franca Maria Bert...; Vittoria Cicaloni; Giovanni Inzalaco; Mattia Cicogni; Laura Tinti; Laura Calabrese; Virginia Barone; Laura Salvini; Pietro Rubegni; Federico Galvagni; Mario Chiariello
• Keywords: KEAP1

Oxidation processes in mitochondria and different environmental insults contribute to unwarranted accumulation of reactive oxygen species (ROS). These, turn, rapidly damage intracellular lipids, proteins, DNA, ultimately causing aging several human diseases. Cells have developed very effective systems control ROS levels. Among these, removal excessive amounts is guaranteed by upregulated expression various antioxidant enzymes, through activation the NF-E2-Related Factor 2 (NRF2) protein. Here, we show that Mitogen Activated Protein Kinase 15 (MAPK15) controls transactivating potential NRF2 and, its downstream target genes. Specifically, upon oxidative stress, MAPK15 necessary increase nuclear translocation, inducing activating phosphorylation, supporting transactivation cytoprotective Lungs are continuously exposed damages induced such as air pollutants cigarette smoke. Interestingly, demonstrate NRF2-dependent transcriptional response smoke epithelial lung cells. Oxidative indeed represents a leading cause disability death worldwide contributing pathogenesis chronic respiratory diseases cancer. Therefore, development novel therapeutic strategies able modulate cellular responses stress would be highly beneficial. Our data understanding molecular mechanisms behind identify new potentially actionable targets.