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Regulation of localization and function of the transcriptional co-activator YAP by angiomotin

Susana Moleirinho1, Sany Hoxha1, Vinay Mandati1

  • 1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, United States.

Elife
|May 4, 2017
PubMed

Insights

Angiomotin (Amot) phosphorylation at Serine 176 regulates the Hippo-YAP pathway. This modification alters Amot-YAP complex localization, impacting cell proliferation and tumorigenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The Hippo-YAP pathway controls cell proliferation, apoptosis, and tissue growth.
  • Angiomotin (Amot) has conflicting reported roles in regulating YAP activity.
  • Understanding Amot's precise function is crucial for deciphering YAP pathway regulation.

Purpose of the Study:

  • To elucidate the role of Angiomotin (Amot) in the Hippo-YAP signaling pathway.
  • To investigate how Amot phosphorylation affects YAP localization and activity.
  • To determine the impact of Amot-YAP complex dynamics on cell proliferation and tumorigenesis.

Main Methods:

  • Co-immunoprecipitation to identify Amot-dependent complexes.
  • Western blotting to assess protein phosphorylation.
  • Immunofluorescence microscopy to determine subcellular localization.
  • Reporter assays to measure YAP target gene transcription.

Main Results:

  • An Amot-dependent complex including YAP and Merlin was identified.
  • Phosphorylation of Amot at Serine 176 (pAmotS176) localized the complex to the plasma membrane.
  • Hypophosphorylated Amot localized the complex to the nucleus, promoting YAP-TEAD interaction and target gene activation.
  • pAmotS176 suppressed YAP-driven proliferation and tumorigenesis by controlling complex localization.

Conclusions:

  • Amot phosphorylation at Serine 176 is a key regulatory mechanism.
  • Amot phosphorylation dictates the subcellular localization of the Amot-YAP complex.
  • This localization switch critically controls YAP activity, cell proliferation, and tumorigenesis.
Keywords:
AngiomotinHippoYAPcancer biologycell biologyhumanmouse

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