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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
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Angiomotin-like proteins associate with and negatively regulate YAP1

Wenqi Wang1, Jun Huang, Junjie Chen

  • 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|December 29, 2010
PubMed

Insights

New research reveals angiomotin-like proteins (AMOTL1 and AMOTL2) regulate the Yes-associated protein YAP1. These interactions control YAP1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The Hippo pathway regulates organ size by controlling cell proliferation and apoptosis.
  • Yes-associated protein YAP1 is a key transcriptional coactivator in this pathway.
  • YAP1 activity is modulated by its nuclear-cytoplasmic localization, dependent on phosphorylation.

Purpose of the Study:

  • To identify new YAP1-associated proteins.
  • To elucidate novel mechanisms regulating YAP1.
  • To investigate the role of angiomotin-like proteins in YAP1 function.

Main Methods:

  • Co-immunoprecipitation to identify YAP1-binding proteins.
  • Western blotting to assess protein interactions and localization.
  • Cell culture experiments (MCF10A cells) to study phenotypic changes.

Main Results:

  • Angiomotin-like protein 1 (AMOTL1) and angiomotin-like protein 2 (AMOTL2) were identified as YAP1-binding proteins.
  • AMOTL1 and AMOTL2 directly interact with YAP1, regulating its translocation between the cytoplasm and nucleus.
  • This regulation is independent of YAP1 phosphorylation.
  • AMOTL2 downregulation in MCF10A cells induced epithelial-mesenchymal transition (EMT), similar to YAP1 overexpression.

Conclusions:

  • A novel mechanism for YAP1 regulation involves direct interaction with AMOTL1 and AMOTL2.
  • Angiomotin-like proteins modulate YAP1 activity and cellular processes like EMT.
  • These findings provide new insights into Hippo pathway signaling and organ size control.

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