| First Author | Shirakawa J | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 4 | Pages | 868-882.e5 |
| PubMed ID | 28286049 | Mgi Jnum | J:240675 |
| Mgi Id | MGI:5888927 | Doi | 10.1016/j.cmet.2017.02.004 |
| Citation | Shirakawa J, et al. (2017) Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic beta Cell Proliferation. Cell Metab 25(4):868-882.e5 |
| abstractText | Investigation of cell-cycle kinetics in mammalian pancreatic beta 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 beta 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 beta cell proliferation and survival. CENP-A deficiency in beta 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 beta cell adaptation to delay and/or prevent progression to diabetes. |
