title: Yes-Associated Protein is up-regulated by mechanical overload and is sufficient to induce skeletal muscle hypertrophy.
abstract: Mechanically-induced skeletal muscle growth is regulated by mammalian/mechanistic target of rapamycin complex 1 (mTORC1). Yes-Associated Protein (YAP) is a mechanically-sensitive, and growth-related, transcriptional co-activator that can regulate mTORC1. Here we show that, in skeletal muscle, mechanical overload promotes an increase in YAP expression; however, the time course of YAP expression is markedly different from that of mTORC1 activation. We also show that the overexpression of YAP induces hypertrophy via an mTORC1-independent mechanism. Finally, we provide preliminary evidence of possible mediators of YAP-induced hypertrophy (e.g. increased MyoD and c-Myc expression, and decreased Smad2/3 activity and muscle ring finger 1 (MuRF1) expression).
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: craig.goodman@vu.edu.au.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Goodman
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Dietz
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Jacobs
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McNally
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: You
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D005260:Female; D005786:Gene Expression Regulation; D006984:Hypertrophy; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D051899:Smad2 Protein; D051900:Smad3 Protein; D000070584:Tripartite Motif Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Hippo pathway; Mammalian/mechanistic target of rapamycin complex 1; Mechanotransduction; Synergist ablation; TEA domain; Yes-Associated Protein