ArticleJournal of cell science2020
Gain-of-function genetic screen of the kinome reveals BRSK2 as an inhibitor of the NRF2 transcription factor.
Article in Journal of cell science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Proteomic Profile of Skeletal Muscles and Liver in a Dexamethasone-Induced Atrophy Model: Insights into the Role of β-Hydroxy-β-Methylbutyrate on Contractile and Metabolic Protein.Cell biochemistry and biophysics · 2026Article
- Suicide risk genes impact evolutionarily conserved survival strategies.Translational psychiatry · 2026Article
- The PI3K pathway is a downstream effector of NRF2 activation in the esophagus.Translational oncology · 2026Article
- BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.Scientific reports · 2025Article
- Suicide risk genes impact evolutionarily conserved survival strategies.Research square · 2025Article
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- Article
- Redox Regulation of Brain Selective Kinases BRSK1/2: Implications for Dynamic Control of the Eukaryotic AMPK family through Cys-based mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Illuminating function of the understudied druggable kinome.Drug discovery today · 2024Review
- BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes.Journal of molecular cell biology · 2023Article
- Dynamic Regulation ofInternational journal of molecular sciences · 2023Article
- Principles of phosphoproteomics and applications in cancer research.The Biochemical journal · 2023Article
- Case report: A novel frameshift mutation in BRSK2 causes autism in a 16-year old Chinese boy.Frontiers in psychiatry · 2023Article
- Protein proximity networks and functional evaluation of the casein kinase 1 gamma family reveal unique roles for CK1γ3 in WNT signaling.The Journal of biological chemistry · 2022Article
- The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells.Cell death discovery · 2022Article
- Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors.Translational psychiatry · 2021Article
- Article
- The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases.Nucleic acids research · 2021Article
- PKIS deep dive yields a chemical starting point for dark kinases and a cell active BRSK2 inhibitor.Scientific reports · 2020Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, but conversely NRF2 activity diminishes with age and in neurodegenerative and metabolic disorders. Although NRF2-activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here, we describe use of a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the under-studied protein kinase brain-specific kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives 5'-AMP-activated protein kinase α2 (AMPK) signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppresses ribosome-RNA complexes, global protein synthesis and NRF2 protein levels. Collectively, our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis might prove useful for therapeutically targeting NRF2 in human disease.This article has an associated First Person interview with the first author of the paper.
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