ArticleNature cell biology2009
The CDK4-pRB-E2F1 pathway controls insulin secretion.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 127 citations in OpenAlex.
- Chronic NHScientific reports · 2026Article
- E2F1 K117 methylation by SETD6 disrupts BRD4-E2F1 binding and modulates E2F1 chromatin binding and gene regulation in prostate cancer cells.Nucleic acids research · 2026Article
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- CDK-4 regulates nucleolar size and metabolism at the cost of late-life fitness in C. elegans.Heredity · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Tanycytic transcytosis inhibition disrupts energy balance, glucose homeostasis and cognitive function in male mice.Molecular metabolism · 2024Article
- Effects of nutrient metabolism on pancreatic β-cell mass and function: Recent findings.Journal of diabetes investigation · 2023Article
- Nedd4L suppression in lung fibroblasts facilitates pathogenesis of lung fibrosis.Translational research : the journal of laboratory and clinical medicine · 2023Article
- Article
- E2F1 transcription factor mediates a link between fat and islets to promote β cell proliferation in response to acute insulin resistance.Cell reports · 2022Article
- Article
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- The Temporal Profile of Circulating miRNAs during Gestation in Overweight and Obese Women with or without Gestational Diabetes Mellitus.Biomedicines · 2022Article
- Hypophosphorylated pRb knock-in mice exhibit hallmarks of aging and vitamin C-preventable diabetes.The EMBO journal · 2022Article
- Article
- Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function.Nature metabolism · 2021Article
- Article
- The multifaceted role of cell cycle regulators in the coordination of growth and metabolism.The FEBS journal · 2021Review
- Progenitor-like characteristics in a subgroup of UCP1+ cells within white adipose tissue.Developmental cell · 2021Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK4-pRB-E2F1 cell-cycle regulators are robustly expressed in non-proliferating beta cells, suggesting that besides the control of beta-cell number the CDK4-pRB-E2F1 pathway has a role in beta-cell function. We show here that E2F1 directly regulates expression of Kir6.2, which is a key component of the K(ATP) channel involved in the regulation of glucose-induced insulin secretion. We demonstrate, through chromatin immunoprecipitation analysis from tissues, that Kir6.2 expression is regulated at the promoter level by the CDK4-pRB-E2F1 pathway. Consistently, inhibition of CDK4, or genetic inactivation of E2F1, results in decreased expression of Kir6.2, impaired insulin secretion and glucose intolerance in mice. Furthermore we show that rescue of Kir6.2 expression restores insulin secretion in E2f1(-/-) beta cells. Finally, we demonstrate that CDK4 is activated by glucose through the insulin pathway, ultimately resulting in E2F1 activation and, consequently, increased expression of Kir6.2. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis, defining a new link between cell proliferation and metabolism.
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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.