ArticleMolecular endocrinology (Baltimore, Md.)2009
p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Stimulation to secrete insulin induces pancreatic β-cell dysfunction through Tfe3 activation.iScience · 2026Article
- Enhanced Insulin Secretion Through Upregulation of Transcription Factors by Hydroalcoholic Extract of Securigera securidaca Seeds in Diabetic Animal Model.Endocrinology, diabetes & metabolism · 2024Article
- The ubiquitin ligase HERC4 suppresses MafA transcriptional activity triggered by GSK3β in myeloma by atypical K63-linked polyubiquitination.The Journal of biological chemistry · 2023Article
- Spatial and transcriptional heterogeneity of pancreatic beta cell neogenesis revealed by a time-resolved reporter system.Diabetologia · 2022Article
- Role of the Transcription Factor MAFA in the Maintenance of Pancreatic β-Cells.International journal of molecular sciences · 2022Review
- MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms.Biomolecules · 2022Review
- Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus.Frontiers in endocrinology · 2022Review
- Redox Homeostasis in Pancreatic β-Cells: From Development to Failure.Antioxidants (Basel, Switzerland) · 2021Review
- p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells.International journal of molecular sciences · 2021Article
- Oxidative stress and diabetes: antioxidative strategies.Frontiers of medicine · 2020Review
- Beta cell identity changes with mild hyperglycemia: Implications for function, growth, and vulnerability.Molecular metabolism · 2020Article
- Reversal of angiotensin ll-induced β-cell dedifferentiation via inhibition of NF-κb signaling.Molecular medicine (Cambridge, Mass.) · 2018Article
- MAFb protein confers intrinsic resistance to proteasome inhibitors in multiple myeloma.BMC cancer · 2018Article
- Distinct Shift in Beta-Cell Glutaredoxin 5 Expression Is Mediated by Hypoxia and Lipotoxicity BothFrontiers in endocrinology · 2018Article
- The undoing and redoing of the diabetic β-cell.Journal of diabetes and its complications · 2017Review
- The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus.Antioxidants & redox signaling · 2017Review
- Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.Best practice & research. Clinical endocrinology & metabolism · 2015Review
- Aldosterone induces clonal β-cell failure through glucocorticoid receptor.Scientific reports · 2015Article
- Heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion, but not insulin action, in high-fat-fed mice.Diabetes · 2014Article
- Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA.Developmental biology · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Mammalian MafA/RIPE3b1 is an important glucose-responsive transcription factor that regulates function, maturation, and survival of beta-cells. Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function. Because MafA is a highly phosphorylated protein, we examined whether regulating activity of protein kinases can increase MafA expression by enhancing its stability. We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3. Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose. We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation. Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK. Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA. These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations. Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.