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Author Notes:

Address correspondence to: Asma Nusrat (anusrat@emory.edu).

We thank Caroline Addis and Susan Voss for expert technical assistance.


Research Funding:

This work was supported by grants from the National Institutes of Health (DK72564, DK61379, and DK79392 to C.P.; DK53202, DK55679, and DK59888 to A.N.; and DK64399 [NIH Digestive Diseases Research Consortium tissue culture and morphology grant]) and the Crohn's and Colitis Foundation of America (fellowship award to S.K., and C.T.C.).

Tight function zonula occludens-3 regulates cyclin D1–dependent cell proliferation


Journal Title:

Molecular Biology of the Cell


Volume 22, Number 10


, Pages 1677-1685

Type of Work:

Article | Final Publisher PDF


ABSTRACT: 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 G0/G1 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.

Copyright information:

© 2011 Capaldo et al. This article is distributed by The American Society for Cell Biology under license from the author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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