title: Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1.
abstract: Tissue homeostasis is controlled by signaling systems that coordinate cell proliferation, cell growth and cell shape upon changes in the cellular environment. Deregulation of these processes is associated with human cancer and can occur at multiple levels of the underlying signaling systems. To gain an integrated view on signaling modules controlling tissue growth, we analyzed the interaction proteome of the human Hippo pathway, an established growth regulatory signaling system. The resulting high-resolution network model of 480 protein-protein interactions among 270 network components suggests participation of Hippo pathway components in three distinct modules that all converge on the transcriptional co-activator YAP1. One of the modules corresponds to the canonical Hippo kinase cassette whereas the other two both contain Hippo components in complexes with cell polarity proteins. Quantitative proteomic data suggests that complex formation with cell polarity proteins is dynamic and depends on the integrity of cell-cell contacts. Collectively, our systematic analysis greatly enhances our insights into the biochemical landscape underlying human Hippo signaling and emphasizes multifaceted roles of cell polarity complexes in Hippo-mediated tissue growth control.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Hauri
authors.forename: Alexander
authors.initials: A
authors.lastname: Wepf
authors.forename: Audrey
authors.initials: A
authors.lastname: van Drogen
authors.forename: Markku
authors.initials: M
authors.lastname: Varjosalo
authors.forename: Nic
authors.initials: N
authors.lastname: Tapon
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Matthias
authors.initials: M
authors.lastname: Gstaiger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002450:Cell Communication; D016764:Cell Polarity; D016000:Cluster Analysis; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D020543:Proteome; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases