Abstract
The Hippo pathway controls metazoan organ growth by regulating cell proliferation and apoptosis. Many components have been identified, but our knowledge of the composition and structure of this pathway is still incomplete. Using existing pathway components as baits, we generated by mass spectrometry a high-confidence Drosophila Hippo protein-protein interaction network (Hippo-PPIN) consisting of 153 proteins and 204 interactions. Depletion of 67% of the proteins by RNA interference regulated the transcriptional coactivator Yorkie (Yki) either positively or negatively. We selected for further characterization a new member of the alpha-arrestin family, Leash, and show that it promotes degradation of Yki through the lysosomal pathway. Given the importance of the Hippo pathway in tumor development, the Hippo-PPIN will contribute to our understanding of this network in both normal growth and cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Protein Interaction Maps*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proteome / genetics
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Proteome / metabolism
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RNA Interference
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / metabolism
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YAP-Signaling Proteins
Substances
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Proteome
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Trans-Activators
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YAP-Signaling Proteins
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Yki protein, Drosophila
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Protein Serine-Threonine Kinases
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hpo protein, Drosophila