ArticleThe Journal of clinical investigation2022
Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Harmine selectively enhances human beta cell identity markers and function via protein kinase A pathways.Diabetologia · 2026Article
- Mapping the Brain Interaction Network of the Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Targeted by Leucettinib-21 Using Affinity Chromatography.ACS pharmacology & translational science · 2026Article
- Dose-resolved control of somatic reprogramming by Rora.Stem cell reports · 2026Article
- Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies.Biomolecules & therapeutics · 2025Review
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis.Nucleic acids research · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Review
- The E2F4 transcriptional repressor is a key mechanistic regulator of colon cancer resistance tobioRxiv : the preprint server for biology · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Emerging Role of the DREAM Complex in Cancer and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors.Cell reports. Medicine · 2024Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Scaling Insulin-Producing Cells by Multiple Strategies.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome.Science translational medicine · 2024Article
- Development, regeneration, and physiological expansion of functional β-cells: Cellular sources and regulators.Frontiers in cell and developmental biology · 2024Review
- Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus.Frontiers in endocrinology · 2024Review
- Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.JCI insight · 2023Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Resistance to regeneration of insulin-producing pancreatic β cells is a fundamental challenge for type 1 and type 2 diabetes. Recently, small molecule inhibitors of the kinase DYRK1A have proven effective in inducing adult human β cells to proliferate, but their detailed mechanism of action is incompletely understood. We interrogated our human insulinoma and β cell transcriptomic databases seeking to understand why β cells in insulinomas proliferate, while normal β cells do not. This search reveals the DREAM complex as a central regulator of quiescence in human β cells. The DREAM complex consists of a module of transcriptionally repressive proteins that assemble in response to DYRK1A kinase activity, thereby inducing and maintaining cellular quiescence. In the absence of DYRK1A, DREAM subunits reassemble into the pro-proliferative MMB complex. Here, we demonstrate that small molecule DYRK1A inhibitors induce human β cells to replicate by converting the repressive DREAM complex to its pro-proliferative MMB conformation.
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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.