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The Hippo signaling pathway interactome.

Young Kwon1, Arunachalam Vinayagam, Xiaoyun Sun

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Researchers mapped the Hippo pathway's protein interactions, identifying 153 proteins and 204 interactions. A new protein, Leash, was found to degrade Yorkie, impacting organ growth and cancer.

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Area of Science:

  • Cell biology
  • Developmental biology
  • Molecular biology

Background:

  • The Hippo pathway is crucial for regulating organ size by controlling cell proliferation and apoptosis.
  • Despite its importance, the complete composition and structure of the Hippo pathway remain incompletely understood.

Purpose of the Study:

  • To construct a comprehensive protein-protein interaction network (Hippo-PPIN) for the Drosophila Hippo pathway.
  • To identify novel components and regulatory mechanisms within the Hippo pathway.

Main Methods:

  • Utilized mass spectrometry with existing Hippo pathway components as baits to generate the Hippo-PPIN.
  • Employed RNA interference (RNAi) to assess the functional impact of identified proteins on the transcriptional coactivator Yorkie (Yki).
  • Selected and characterized a novel alpha-arrestin family member, Leash.

Main Results:

  • Generated a high-confidence Hippo-PPIN comprising 153 proteins and 204 interactions.
  • RNAi screening revealed that depletion of 67% of the identified proteins affects Yorkie (Yki) activity either positively or negatively.
  • Identified Leash as a novel regulator that promotes the degradation of Yorkie (Yki) via the lysosomal pathway.

Conclusions:

  • The generated Hippo-PPIN provides a valuable resource for understanding Hippo pathway composition and function.
  • Leash represents a newly discovered component that negatively regulates the Hippo pathway by targeting Yorkie (Yki) for degradation.
  • This research deepens the understanding of the Hippo pathway's role in normal organ growth and its implications in cancer development.