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Updated: Apr 14, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

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NOS1AP Functionally Associates with YAP To Regulate Hippo Signaling

Leanne Clattenburg1, Michael Wigerius1, Jiansong Qi1

  • 1Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.

Molecular and Cellular Biology
|April 29, 2015
PubMed

Insights

Nitric oxide synthase 1 adaptor protein (NOS1AP) isoforms regulate cell growth by interacting with the Hippo signaling pathway. This discovery suggests NOS1AP acts as a tumor suppressor, impacting cell proliferation and oncogenic progression.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Deregulation of cellular polarity proteins impacts cell migration and proliferation.
  • Nitric oxide synthase 1 adaptor protein (NOS1AP) interacts with Scribble, influencing cell migration and oncogenic transformation.
  • The precise link between NOS1AP and signaling pathways controlling oncogenic progression remains unclear.

Purpose of the Study:

  • Identify novel NOS1AP isoforms and their cellular localizations.
  • Investigate the interaction of NOS1AP with the Hippo signaling pathway.
  • Elucidate the role of NOS1AP in regulating cell proliferation and tumor suppression.

Main Methods:

  • Identification of novel NOS1AP isoforms (NOS1APd, NOS1APe, NOS1APf).
  • Analysis of protein-protein interactions, including NOS1AP with Scribble and YAP.
  • Assessment of protein phosphorylation (YAP, Lats1) and transcriptional activity (TEAD) upon NOS1AP modulation.
  • Cellular localization studies of NOS1AP isoforms.

Main Results:

  • Discovered novel NOS1AP isoforms with distinct cellular localizations.
  • Demonstrated that specific NOS1AP isoforms bind Scribble and acidic phospholipids via a PTB domain.
  • Identified a NOS1AP-YAP complex, linking NOS1AP to the Hippo signaling pathway.
  • Showed that NOS1AP silencing decreases YAP and Lats1 phosphorylation, while NOS1AP expression increases it, reducing TEAD activity and cell proliferation.

Conclusions:

  • NOS1AP isoforms play a role in regulating cell polarity and membrane interactions.
  • NOS1AP is a key component of the Hippo signaling pathway, modulating YAP and Lats1 activity.
  • NOS1AP functions as a tumor suppressor by restricting cell proliferation through Hippo pathway regulation.

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