title: The Hippo signal transduction network in skeletal and cardiac muscle.
abstract: The discovery of the Hippo pathway can be traced back to two areas of research. Genetic screens in fruit flies led to the identification of the Hippo pathway kinases and scaffolding proteins that function together to suppress cell proliferation and tumor growth. Independent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads. Additionally, many other signal transduction proteins crosstalk to members of the Hippo pathway forming a Hippo signal transduction network. We discuss evidence that the Hippo signal transduction network plays important roles in myogenesis, regeneration, muscular dystrophy, and rhabdomyosarcoma in skeletal muscle, as well as in myogenesis, organ size control, and regeneration of the heart. Understanding the role of Hippo kinases in skeletal and heart muscle physiology could have important implications for translational research.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Health Sciences Building, Foresterhill, AB25 2ZD Aberdeen, Scotland, UK. h.wackerhage@abdn.ac.uk.
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
authors.affiliation: Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Del Re
authors.affiliation: School of Medical Sciences, University of Aberdeen, Health Sciences Building, Foresterhill, AB25 2ZD Aberdeen, Scotland, UK. Biomedical Research Centre, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Judson
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Republic of Singapore. Department of Medicine, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.
authors.forename: Marius
authors.initials: M
authors.lastname: Sudol
authors.affiliation: Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology / Q000502:physiology*; D000090683:Hippo Signaling Pathway; D006801:Humans; D008958:Models, Molecular; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases