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http://purl.uniprot.org/citations/30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30061109http://www.w3.org/2000/01/rdf-schema#comment"Myofibril breakdown is a fundamental cause of muscle wasting and inevitable sequel of aging and disease. We demonstrated that myofibril loss requires depolymerization of the desmin cytoskeleton, which is activated by phosphorylation. Here, we developed a mass spectrometry-based kinase-trap assay and identified glycogen synthase kinase 3-β (GSK3-β) as responsible for desmin phosphorylation. GSK3-β inhibition in mice prevented desmin phosphorylation and depolymerization and blocked atrophy upon fasting or denervation. Desmin was phosphorylated by GSK3-β 3 d after denervation, but depolymerized only 4 d later when cytosolic Ca2+ levels rose. Mass spectrometry analysis identified GSK3-β and the Ca2+-specific protease, calpain-1, bound to desmin and catalyzing its disassembly. Consistently, calpain-1 down-regulation prevented loss of phosphorylated desmin and blocked atrophy. Thus, phosphorylation of desmin filaments by GSK3-β is a key molecular event required for calpain-1-mediated depolymerization, and the subsequent myofibril destruction. Consequently, GSK3-β represents a novel drug target to prevent myofibril breakdown and atrophy."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.org/dc/terms/identifier"doi:10.1083/jcb.201802018"xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/author"Cohen S."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/author"Volodin A."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/author"Aweida D."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/author"Rudesky I."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/author"Shimko E."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/name"J Cell Biol"xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/pages"3698-3714"xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/title"GSK3-beta promotes calpain-1-mediated desmin filament depolymerization and myofibril loss in atrophy."xsd:string
http://purl.uniprot.org/citations/30061109http://purl.uniprot.org/core/volume"217"xsd:string
http://purl.uniprot.org/citations/30061109http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30061109
http://purl.uniprot.org/citations/30061109http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/30061109
http://purl.uniprot.org/uniprot/#_A0A338P6P8-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_A0A494BAC4-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
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http://purl.uniprot.org/uniprot/#_O35350-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_E9QAQ5-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_Q3TI07-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_Q3V2C6-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_Q3UDG8-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109
http://purl.uniprot.org/uniprot/#_Q80Y25-mappedCitation-30061109http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30061109