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ZO proteins redundantly regulate the transcription factor DbpA/ZONAB
Domenica Spadaro1, Rocio Tapia1, Lionel Jond1
1From the Department of Cell Biology, University of Geneva, 1211 Geneva, Switzerland.
The Journal of Biological Chemistry
|July 3, 2014
Summary
Tight junction proteins ZO-1 and ZO-2 regulate DbpA stability at cell junctions and YAP nuclear import. ZO proteins redundantly control DbpA localization without impacting its nuclear transport.
Area of Science:
- Cell Biology
- Molecular Biology
- Epithelial Biology
Background:
- Epithelial junction assembly regulates transcription factors DbpA/ZONAB and YAP.
- A model proposed ZO-1 sequesters DbpA at tight junctions (TJs) to inhibit proliferation.
- This model is contradicted by ZO-1 knockout studies showing no increased proliferation.
Purpose of the Study:
- To investigate the roles of ZO-1, ZO-2, and ZO-3 in regulating DbpA and YAP.
- To resolve discrepancies regarding ZO-1's function in DbpA regulation and cell proliferation.
Main Methods:
- Depletion of ZO proteins (ZO-1, ZO-2, ZO-3) in Madin-Darby canine kidney cells.
- Analysis of DbpA and YAP localization and activity.
- Examination of ZO-1 knockout mammary epithelial cells (Eph4).
- In vitro binding assays.
Main Results:
- Depletion of ZO-1 and ZO-2 increased cytoplasmic DbpA localization.
- Only ZO-2 depletion reduced YAP nuclear import.
- ZO-1 knockout cells retained junctional DbpA.
- Combined ZO-1 and ZO-2 depletion in Eph4 cells decreased DbpA stability, rescued by MG132.
- ZO-1 does not directly bind DbpA.
Conclusions:
- ZO-2 regulates YAP nuclear shuttling.
- ZO proteins (ZO-1, ZO-2, ZO-3) redundantly control DbpA's junctional retention and stability.
- DbpA's nuclear transport is independent of ZO protein regulation.
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