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Updated: Jun 9, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

19.7K

A ZO-2 scaffolding mechanism regulates the Hippo signalling pathway

Olivia Xuan Liu1,2, Lester Bocheng Lin1, Soumya Bunk1,2

  • 1Mechanobiology Institute, National University of Singapore, Singapore.

The FEBS Journal
|October 27, 2024
PubMed

Insights

The tight junction protein ZO-2 is essential for contact inhibition of proliferation by regulating the Hippo signaling pathway. ZO-2 promotes YAP inactivation, maintaining cell density control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Contact inhibition of proliferation is a crucial mechanism for controlling cell density.
  • The Hippo signaling pathway and its downstream effector YAP regulate this process.
  • The precise molecular mechanisms linking cell density cues to Hippo pathway activation are not fully understood.

Purpose of the Study:

  • To investigate the role of the tight junction protein ZO-2 in contact inhibition of proliferation.
  • To elucidate how ZO-2 regulates the Hippo signaling pathway and YAP.
  • To understand the molecular basis of ZO-2 mediated Hippo pathway regulation.

Main Methods:

  • Investigated the necessity of ZO-2 for contact-mediated inhibition of proliferation.
  • Assessed the regulation of Hippo kinase LATS1 and YAP by ZO-2.
  • Utilized ZO-2's scaffolding function (SH3 and PDZ domains) to study YAP phosphorylation by LATS1.

Main Results:

  • ZO-2 is required for contact inhibition of proliferation.
  • ZO-2 regulates LATS1 and YAP.
  • ZO-2's scaffolding function facilitates LATS1-mediated YAP phosphorylation, leading to YAP cytoplasmic retention and inactivation.

Conclusions:

  • ZO-2 is a key regulator of the Hippo signaling pathway.
  • ZO-2 maintains Hippo pathway activation by stabilizing LATS1, thereby inactivating YAP.
  • This mechanism highlights ZO-2's critical role in cell density control.
Keywords:
Hippo signallingtight junction

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