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The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity

Chrysiis Michaloglou1, Waltraut Lehmann, Typhaine Martin

  • 1Novartis Institutes for BioMedical Research, Disease Area Oncology, Basel, Switzerland.

Plos One
|April 25, 2013
PubMed

Insights

Protein tyrosine phosphatase non-receptor type 14 (PTPN14) negatively regulates the Hippo pathway

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Hippo (Hpo) pathway is a critical regulator of organ size.
  • Dysregulation of the Hpo pathway is implicated in human cancers.
  • YAP is a transcriptional co-activator inhibited by the Hpo pathway.

Purpose of the Study:

  • To identify novel regulators of YAP.
  • To elucidate the mechanism by which PTPN14 modulates YAP activity.
  • To investigate the role of PTPN14 in cancer development.

Main Methods:

  • Yeast three-hybrid screening
  • Co-immunoprecipitation
  • Western blotting
  • Cellular localization studies
  • Mammary epithelial cell transformation assays

Main Results:

  • PTPN14 was identified as a YAP-binding protein.
  • PTPN14 negatively regulates YAP activity by controlling its cellular localization.
  • The WW and PPxY motifs mediate YAP-PTPN14 interaction.
  • PTPN14 phosphatase activity and PPxY motif are dispensable for endogenous YAP regulation.
  • PTPN14 downregulation mimics YAP activation and promotes oncogenic transformation in mammary epithelial cells.

Conclusions:

  • PTPN14 is a novel negative regulator of YAP.
  • PTPN14 plays a significant role in Hpo pathway signaling and oncogenesis.
  • Targeting PTPN14 may offer therapeutic strategies for YAP-driven cancers.

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