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The tight junction protein ZO-2 blocks cell cycle progression and inhibits cyclin D1 expression

Lorenza Gonzalez-Mariscal1, Rocio Tapia, Miriam Huerta

  • 1Department of Physiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City, Mexico. lorenza@fisio.cinvestav.mx

Annals of the New York Academy of Sciences
|June 23, 2009
PubMed

Insights

The adaptor protein ZO-2 (Zonula Occludens 2) negatively regulates cyclin D1 transcription and cell proliferation by interacting with c-Myc. This interaction diminishes cyclin D1 protein expression and slows cell growth in epithelial cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Interactions

Background:

  • ZO-2 is a MAGUK family adaptor protein found at tight junctions.
  • ZO-2 exhibits dual localization, present at cell borders and nuclei in sparse cultures, and concentrated at cell boundaries in confluent cultures.

Purpose of the Study:

  • To investigate the role of ZO-2 in regulating cyclin D1 (CD1) expression.
  • To determine if ZO-2 influences epithelial cell proliferation.

Main Methods:

  • Studied ZO-2's effect on CD1 transcription and protein levels.
  • Utilized ZO-2 transfection in MDCK cells.
  • Assessed cell proliferation using a wound-healing assay.

Main Results:

  • ZO-2 negatively regulates CD1 transcription via interaction with c-Myc at the CD1 promoter's E box.
  • ZO-2 transfection led to reduced CD1 protein expression in MDCK cells.
  • ZO-2 expression decreased the rate of cell proliferation in wound-healing assays.

Conclusions:

  • ZO-2 acts as a negative regulator of cyclin D1 expression.
  • ZO-2 plays a role in controlling epithelial cell proliferation.

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