CYLD negatively regulates Hippo signaling by limiting Hpo phosphorylation in Drosophila

Yan Chen1, Zaizhu Wang1, Ping Wang1

  • 1State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.

Insights

Cylindromatosis (CYLD) negatively regulates the Hippo pathway in fruit flies. This deubiquitinase limits Hippo signaling, impacting animal development and providing new insights into CYLD

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Cylindromatosis (CYLD) is a deubiquitinase involved in various cellular processes, including inflammation, apoptosis, and tumorigenesis.
  • While CYLD's biochemical functions are known, its role in animal development is largely uncharacterized.

Purpose of the Study:

  • To investigate the role of Drosophila CYLD (dCYLD) in animal development.
  • To determine if dCYLD interacts with or regulates the Hippo signaling pathway.

Main Methods:

  • Immunoprecipitation and colocalization assays to study dCYLD and Hpo interaction.
  • Western blotting to assess phosphorylation levels of Hpo and Yki.
  • Analysis of Hippo pathway activity in the presence of dCYLD.

Main Results:

  • dCYLD was identified as a negative regulator of the Hippo pathway in vivo.
  • dCYLD associates and colocalizes with Hpo in the cytoplasm.
  • dCYLD limits Hpo activity by reducing its phosphorylation at T195, consequently increasing the activity of its downstream effector, Yki.

Conclusions:

  • dCYLD acts as a negative regulator of the Hippo pathway in Drosophila.
  • This study reveals a novel function for CYLD in regulating animal development through the Hippo signaling cascade.

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