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Updated: Aug 17, 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

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YAP-VGLL4 antagonism defines the major physiological function of the Hippo signaling effector YAP

Jing Cai1, Kyungsuk Choi1, Hongde Li1

  • 1Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Genes & Development
|December 15, 2022
PubMed

Insights

The Hippo-YAP pathway

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Developmental Biology

Background:

  • The Hippo-YAP signaling pathway is crucial for tissue growth, repair, and cancer.
  • YAP (Yes-associated protein) is a key nuclear effector, activating genes via TEAD transcription factors.
  • Understanding YAP's precise role and regulation is vital for therapeutic interventions.

Purpose of the Study:

  • To investigate the antagonistic relationship between YAP and VGLL4 in Hippo pathway regulation.
  • To determine if VGLL4 inactivation can bypass YAP essentiality in development.
  • To explore the role of YAP-VGLL4 antagonism in liver cancer and regeneration.

Main Methods:

  • Genetic manipulation in mouse models to inactivate YAP and VGLL4.
  • Analysis of liver and lung development in genetically modified mice.
  • Assessment of intrahepatic cholangiocarcinoma formation and liver injury models.

Main Results:

  • YAP's essentiality in liver and lung development can be bypassed by VGLL4 inactivation, indicating YAP antagonizes VGLL4.
  • YAP-VGLL4 antagonism influences Hippo pathway output beyond development.
  • VGLL4 inactivation promotes liver cancer and ameliorates liver damage, with its expression reflecting Hippo pathway activity.

Conclusions:

  • The major function of YAP is to antagonize the corepressor VGLL4.
  • VGLL4-mediated repression is central to Hippo pathway regulation.
  • Modulating YAP-VGLL4 interactions offers therapeutic potential for cancer and regenerative medicine.
Keywords:
Hippo signalingTEADVGLL4YAPdefault repressionregenerationtumor suppressor

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