Zona occludens-2 inhibits cyclin D1 expression and cell proliferation and exhibits changes in localization along the cell cycle

Here, we have studied the effect of the tight junction protein zona occludens (ZO)-2 on cyclin D1 (CD1) protein expression. CD1 is essential for cell progression through the G1 phase of the cell cycle. We have found that in cultures of synchronized Madin-Darby canine kidney cells, ZO-2 inhibits cell...

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Bibliographic Details
Published in:Molecular biology of the cell 2009-02, Vol.20 (3), p.1102-1117
Main Authors: Tapia, Rocio, Huerta, Miriam, Islas, Socorro, Avila-Flores, Antonia, Lopez-Bayghen, Esther, Weiske, Jörg, Huber, Otmar, González-Mariscal, Lorenza
Format: Article
Language:English
Subjects:
Animals
Apoptosis
beta Catenin - metabolism
Cell Cycle
Cell Line
Cell Proliferation
Cyclin D1 - genetics
Cyclin D1 - metabolism
Dogs
Down-Regulation
Gene Expression Regulation
Glycogen Synthase Kinase 3 - metabolism
Humans
Membrane Proteins - metabolism
Models, Biological
Phosphoserine - metabolism
Proteasome Endopeptidase Complex - metabolism
Protein Processing, Post-Translational
Protein Transport
RNA, Messenger - genetics
RNA, Messenger - metabolism
Subcellular Fractions - metabolism
Transfection
Zonula Occludens-2 Protein
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Summary:Here, we have studied the effect of the tight junction protein zona occludens (ZO)-2 on cyclin D1 (CD1) protein expression. CD1 is essential for cell progression through the G1 phase of the cell cycle. We have found that in cultures of synchronized Madin-Darby canine kidney cells, ZO-2 inhibits cell proliferation at G0/G1 and decreases CD1 protein level. These effects occur in response to a diminished CD1 translation and an augmented CD1 degradation at the proteosome triggered by ZO-2. ZO-2 overexpression decreases the amount of Glycogen synthase kinase-3beta phosphorylated at Ser9 and represses beta-catenin target gene expression. We have also explored the expression of ZO-2 through the cell cycle and demonstrate that ZO-2 enters the nucleus at the late G1 phase and leaves the nucleus when the cell is in mitosis. These results thus explain why in confluent quiescent epithelia ZO-2 is absent from the nucleus and localizes at the cellular borders, whereas in sparse proliferating cultures ZO-2 is conspicuously present at the nucleus.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e08-03-0277