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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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Opposing roles of angiomotin-like-1 and zona occludens-2 on pro-apoptotic function of YAP

T Oka1, A P Schmitt, M Sudol

  • 1Laboratory of Signal Transduction and Proteomic Profiling, Weis Center for Research, Geisinger Clinic, Danville, PA, USA.

Oncogene
|June 21, 2011
PubMed

Insights

Angiomotin-like-1 (AmotL1) and zona occludens-2 (ZO-2) proteins form a complex with the Yes-associated protein (YAP) oncogene. AmotL1 inhibits YAP

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncogenesis

Background:

  • Yes-associated protein (YAP) is an oncogene that regulates cell proliferation.
  • YAP forms complexes with Angiomotin (Amot) family proteins, which sequester YAP in the cytoplasm, inhibiting its proliferative function.
  • YAP also interacts with zona occludens-2 (ZO-2), promoting nuclear translocation.

Purpose of the Study:

  • To investigate the interaction between AmotL1, YAP, and ZO-2.
  • To elucidate the opposing regulatory roles of AmotL1 and ZO-2 on YAP function.
  • To identify potential therapeutic targets for controlling YAP's oncogenic activity.

Main Methods:

  • HEK293 cell line was used for experiments.
  • Apoptotic 'read-out' assays were employed to assess YAP function.
  • Protein complex formation was analyzed to understand regulatory mechanisms.

Main Results:

  • AmotL1 binds to YAP via its PPxY motifs, inhibiting nuclear translocation and pro-apoptotic function.
  • ZO-2 promotes YAP nuclear translocation.
  • A tripartite complex of AmotL1, YAP, and ZO-2 was identified, with AmotL1 inhibiting and ZO-2 enhancing YAP's pro-apoptotic function.

Conclusions:

  • AmotL1 and ZO-2 regulate YAP function in opposing directions.
  • The interplay between AmotL1, YAP, and ZO-2 offers potential strategies for controlling YAP's oncogenic function.
  • Further characterization of these regulators is crucial for cancer therapy development.

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