| First Author | Capaldo CT | Year | 2011 |
| Journal | Mol Biol Cell | Volume | 22 |
| Issue | 10 | Pages | 1677-85 |
| PubMed ID | 21411630 | Mgi Jnum | J:182969 |
| Mgi Id | MGI:5317249 | Doi | 10.1091/mbc.E10-08-0677 |
| Citation | Capaldo CT, et al. (2011) Tight function zonula occludens-3 regulates cyclin D1-dependent cell proliferation. Mol Biol Cell 22(10):1677-85 |
| abstractText | Coordinated regulation of cell proliferation is vital for epithelial tissue homeostasis, and uncontrolled proliferation is a hallmark of carcinogenesis. A growing body of evidence indicates that epithelial tight junctions (TJs) play a role in these processes, although the mechanisms involved are poorly understood. In this study, we identify and characterize a novel plasma membrane pool of cyclin D1 with cell-cycle regulatory functions. We have determined that the zonula occludens (ZO) family of TJ plaque proteins sequesters cyclin D1 at TJs during mitosis, through an evolutionarily conserved class II PSD-95, Dlg, and ZO-1 (PDZ)-binding motif within cyclin D1. Disruption of the cyclin D1/ZO complex through mutagenesis or siRNA-mediated suppression of ZO-3 resulted in increased cyclin D1 proteolysis and G(0)/G(1) cell-cycle retention. This study highlights an important new role for ZO family TJ proteins in regulating epithelial cell proliferation through stabilization of cyclin D1 during mitosis. |
