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Updated: Jan 30, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie

Xiaohan Sun1, Yan Ding1, Meixiao Zhan2

  • 1State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.

Nature Communications
|January 26, 2019
PubMed

Insights

The Hippo pathway regulates organ size. This study reveals that Usp7/HAUSP stabilizes Yorkie/Yap, a key Hippo pathway component, impacting cancer development and offering a potential therapeutic target for liver cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The Hippo pathway is crucial for organ development and tissue homeostasis.
  • Dysregulation of the Hippo pathway is linked to various cancers.
  • The regulation of Yorkie (Yki) protein stability, the key effector, remains poorly understood.

Purpose of the Study:

  • To elucidate the mechanism regulating Yorkie (Yki) protein stability within the Hippo signaling pathway.
  • To investigate the role of ubiquitin-specific protease 7 (Usp7) and its homolog HAUSP in Hippo pathway regulation.
  • To explore the potential of HAUSP as a therapeutic target for hepatocellular carcinoma (HCC).

Main Methods:

  • Investigated the interaction between the Hippo pathway and Usp7.
  • Analyzed the effect of Usp7/HAUSP on Yki/Yap ubiquitination and protein stability.
  • Examined the correlation between HAUSP and Yap expression in clinical HCC samples.

Main Results:

  • The Hippo pathway inhibits the binding of Usp7 to Yki, controlling Yki deubiquitination and stability.
  • Mammalian HAUSP regulates the Hippo pathway by modulating Yap ubiquitination and degradation.
  • HAUSP and Yap expression are elevated in HCC tissues, showing a positive correlation.

Conclusions:

  • Usp7/HAUSP stabilizes the Hippo pathway effector Yki/Yap.
  • HAUSP plays a conserved role in Hippo pathway regulation.
  • HAUSP represents a potential therapeutic target for hepatocellular carcinoma.

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