ArticleDevelopmental cell2017
Multi-site Neurogenin3 Phosphorylation Controls Pancreatic Endocrine Differentiation.
Article in Developmental cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- Review
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- Multifaceted functions of transcription regulatory factor X6 (RFX6): from pancreatic development to cancer progression.Cancer cell international · 2025Review
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.Development (Cambridge, England) · 2024Article
- Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation.Cell stem cell · 2024Article
- LINC MIR503HG Controls SC-β Cell Differentiation and Insulin Production by Targeting CDH1 and HES1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The porcine islet-derived organoid showed the characteristics as pancreatic duct.Scientific reports · 2024Article
- Article
- β-Cell Regeneration Is Driven by Pancreatic Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Noncanonical CDK4 signaling rescues diabetes in a mouse model by promoting β cell differentiation.The Journal of clinical investigation · 2023Article
- Arginine 65 methylation of Neurogenin 3 by PRMT1 is required for pancreatic endocrine development of hESCs.Experimental & molecular medicine · 2023Article
- CA 19-9 but Not IGF-1/IGFBP-2 Is a Useful Biomarker for Pancreatic Ductal Adenocarcinoma (PDAC) and Chronic Pancreatitis (CP) Differentiation.Journal of clinical medicine · 2023Article
- Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells.In vitro cellular & developmental biology. Animal · 2023Article
- USP7 controls NGN3 stability and pancreatic endocrine lineage development.Nature communications · 2023Article
- Tmem88 confines ectodermal Wnt2bb signaling in pharyngeal arch artery progenitors for balancing cell cycle progression and cell fate decision.Nature cardiovascular research · 2023Article
- In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells.Scientific reports · 2022Article
- Review
- ASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in pancreatic endocrine cell differentiation, although regulation of Ngn3 protein is largely unexplored. Here we demonstrate that Ngn3 protein undergoes cyclin-dependent kinase (Cdk)-mediated phosphorylation on multiple serine-proline sites. Replacing wild-type protein with a phosphomutant form of Ngn3 increases α cell generation, the earliest endocrine cell type to be formed in the developing pancreas. Moreover, un(der)phosphorylated Ngn3 maintains insulin expression in adult β cells in the presence of elevated c-Myc and enhances endocrine specification during ductal reprogramming. Mechanistically, preventing multi-site phosphorylation enhances both Ngn3 stability and DNA binding, promoting the increased expression of target genes that drive differentiation. Therefore, multi-site phosphorylation of Ngn3 controls its ability to promote pancreatic endocrine differentiation and to maintain β cell function in the presence of pro-proliferation cues and could be manipulated to promote and maintain endocrine differentiation in vitro and in vivo.
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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.