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Updated: Jun 4, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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CDK5 interacts with MST2 and modulates the Hippo signalling pathway.

Mehak Passi1, Jan B Stöckl2, Thomas Fröhlich2

  • 1Center for Drug Research, Ludwig-Maximilians-University Munich, Germany.

FEBS Open Bio
|December 31, 2024
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Summary

The Hippo pathway kinase MST2 interacts with CDK5, revealing CDK5

Keywords:
CDK5HippoTAZYAPyeast‐two‐hybrid

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Area of Science:

  • Cell signaling and molecular biology
  • Cancer research and therapeutics

Background:

  • The Hippo signaling pathway, regulated by MST2 (STK3), controls organ size and tissue homeostasis via YAP/TAZ.
  • Cyclin-dependent kinase 5 (CDK5) is implicated in tumor growth and angiogenesis, with a potential but unclear link to the Hippo pathway.

Purpose of the Study:

  • To elucidate the functional interaction between MST2 and CDK5 within the Hippo signaling pathway.
  • To investigate the role of CDK5 in regulating Hippo pathway components and transcriptional activity of YAP.

Main Methods:

  • Yeast two-hybrid screening to identify novel protein interactions.
  • Co-immunoprecipitation assays to confirm MST2-CDK5 interaction.
  • Cellular knockdown experiments and phosphoproteomics to analyze pathway modulation.

Main Results:

  • A novel interaction between MST2 and CDK5 was identified and confirmed.
  • CDK5 knockdown reduced YAP transcriptional activity and altered phosphorylation of LATS1 and DLG5.
  • CDK5 acts as a signaling hub integrating Hippo pathway with other cascades.

Conclusions:

  • CDK5 directly interacts with and modulates key components of the Hippo pathway, including MST2, LATS1, and DLG5.
  • CDK5's role in regulating YAP activity suggests potential therapeutic strategies targeting CDK5 inhibitors in cancer.