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Tight function zonula occludens-3 regulates cyclin D1-dependent cell proliferation
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Atlanta, GA, USA.
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Atlanta, GA, USA.
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Atlanta, GA, USA.
Yerkes-Microbiology, Emory University, Atlanta, GA, USA.
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2011 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 22, no 10, p. 1677-1685Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Bethesda, United States: American Society for Cell Biology , 2011. Vol. 22, no 10, p. 1677-1685
Keywords [en]
Amino Acid Sequence, Animals, Carrier Proteins/*metabolism, Cell Fractionation, Cell Line, Cell Membrane/metabolism, *Cell Proliferation, Colon/cytology, Cyclin D1/*metabolism, Humans, Intestinal Mucosa/metabolism, Membrane Proteins/*metabolism, Mice, Mice, Inbred C57BL, Mitosis, PDZ Domains, Protein Binding, Protein Interaction Domains and Motifs, Protein Stability, Protein Transport, Recombinant Fusion Proteins/metabolism, Tight Junctions/*metabolism, Zonula Occludens Proteins
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-141652DOI: 10.1091/mbc.E10-08-0677ISI: 000290515600005PubMedID: 21411630Scopus ID: 2-s2.0-79955973354ISBN: 1939-4586 (Electronic) 1059-1524 (Linking) OAI: oai:DiVA.org:liu-141652DiVA, id: diva2:1149716
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2018-02-06Bibliographically approved

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