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Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival. CENP-A deficiency in β cells leads to impaired adaptive proliferation in response to pregnancy, acute and chronic insulin resistance, and aging in mice. Insulin-stimulated CENP-A/PLK1 protein expression is blunted in islets from patients with type 2 diabetes. These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the β cell adaptation to delay and/or prevent progression to diabetes.
Pubmed ID: 28286049 RIS Download
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Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsThis polyclonal targets FOXM1
View all literature mentionsThis monoclonal targets Histone H3, acetyl (Lys9)
View all literature mentionsThis monoclonal targets Cyclin D2 (D52F9) Rabbit mAb
View all literature mentionsThis monoclonal targets PLK1
View all literature mentionsThis unknown targets phospho-Histone H3 (Ser10)
View all literature mentionsThis monoclonal targets cells that have bromodeoxyuridine incorporated in their DNA
View all literature mentionsThis polyclonal targets Insulin
View all literature mentionsThis polyclonal targets Mouse CENPA
View all literature mentionsThis monoclonal targets CENP-A (C5H3) Rabbit mAb (Mouse Specific)
View all literature mentionsThis polyclonal targets SREBF1
View all literature mentionsThis monoclonal targets PEPCK (F-3)
View all literature mentionsThis polyclonal targets FOXM1 (C-20)
View all literature mentionsThis monoclonal targets Cdc2
View all literature mentionsThis monoclonal targets alpha Tubulin antibody [DM1A] - Loading Control
View all literature mentionsThis polyclonal targets LMNB1
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis unknown targets Cyclin B1
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
View all literature mentionsThis polyclonal targets Igf1r
View all literature mentionsThis recombinant monoclonal targets Insulin Receptor beta
View all literature mentionsThis monoclonal targets Histone H3, phospho (Ser10)
View all literature mentionsThis polyclonal targets CENPA
View all literature mentionsThis monoclonal targets CENP-A (C51A7) Rabbit mAb (Mouse Specific; IF Preferred)
View all literature mentionsThis monoclonal targets Histone H3, phospho (Ser28)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsMus musculus with name B6.Cg-Tg(Ins1-cre/ERT)1Lphi/J from IMSR.
View all literature mentionsMus musculus with name B6.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/RainJ from IMSR.
View all literature mentionsThis monoclonal targets Histone H3, acetyl (Lys9)
View all literature mentions
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