ArticleThe Journal of biological chemistry2016
Npas4 Transcription Factor Expression Is Regulated by Calcium Signaling Pathways and Prevents Tacrolimus-induced Cytotoxicity in Pancreatic Beta Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Truncated CD19 as a selection marker for the isolation of stem cell-derived β-cells.Disease models & mechanisms · 2026Article
- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- The universal role of adaptive transcription in health and disease.The FEBS journal · 2025Review
- Tacrolimus and diabetic rodent models.Pharmacological reports : PR · 2025Review
- Tacrolimus induces insulin receptor substrate 1 hyperphosphorylation and inhibits mTORc1/S6K1 cascade in HL7702 cells.World journal of diabetes · 2025Article
- Tracking Insulin- and Glucagon-Expressing Cells In Vitro and In Vivo Using a Double-Reporter Human Embryonic Stem Cell Line.Diabetes · 2025Article
- Identification of genetic associations and functional SNPs of bovine KLF6 gene on milk production traits in Chinese holstein.BMC genomic data · 2023Article
- The functions of CaJournal of cell communication and signaling · 2023Review
- Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Small Molecule-mediated Insulin Hypersecretion Induces Transient ER Stress Response and Loss of Beta Cell Function.Endocrinology · 2022Article
- Dynamic changes in β-cell [CaMolecular metabolism · 2022Article
- Article
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Lrrc55 is a novel prosurvival factor in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2019Article
- bHLH-PAS Proteins: Their Structure and Intrinsic Disorder.International journal of molecular sciences · 2019Review
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
- Multiple sequences orchestrate subcellular trafficking of neuronal PAS domain-containing protein 4 (NPAS4).The Journal of biological chemistry · 2018Article
- A post-translational balancing act: the good and the bad of SUMOylation in pancreatic islets.Diabetologia · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cytosolic calcium influx activates signaling pathways known to support pancreatic beta cell function and survival by modulating gene expression. Impaired calcium signaling leads to decreased beta cell mass and diabetes. To appreciate the causes of these cytotoxic perturbations, a more detailed understanding of the relevant signaling pathways and their respective gene targets is required. In this study, we examined the calcium-induced expression of the cytoprotective beta cell transcription factor Npas4. Pharmacological inhibition implicated the calcineurin, Akt/protein kinase B, and Ca(2+)/calmodulin-dependent protein kinase signaling pathways in the regulation of Npas4 transcription and translation. Both Npas4 mRNA and protein had high turnover rates, and, at the protein level, degradation was mediated via the ubiquitin-proteasome pathway. Finally, beta cell cytotoxicity of the calcineurin inhibitor and immunosuppressant tacrolimus (FK-506) was prevented by Npas4 overexpression. These results delineate the pathways regulating Npas4 expression and stability and demonstrate its importance in clinical settings such as islet transplantation.
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