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 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.
Tapia
Rocio
R
Department of Physiology, Biophysics, and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), Mexico, D.F., 07360, Mexico.
Huerta
Miriam
M
Islas
Socorro
S
Avila-Flores
Antonia
A
Lopez-Bayghen
Esther
E
Weiske
Jörg
J
Huber
Otmar
O
González-Mariscal
Lorenza
L
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D010768:Phosphoserine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D062827:Zonula Occludens-2 Protein; D051176:beta Catenin / Q000378:metabolism
D008565:Membrane Proteins; D012333:RNA, Messenger; C569046:TJP2 protein, human; D062827:Zonula Occludens-2 Protein; D051176:beta Catenin; D019938:Cyclin D1; D010768:Phosphoserine; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex