title: The Hippo signaling pathway interactome.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Kwon
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Vinayagam
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Sun
authors.forename: Noah
authors.initials: N
authors.lastname: Dephoure
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Pengyu
authors.initials: P
authors.lastname: Hong
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D020543:Proteome; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases