{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:44:20Z","timestamp":1791524660455,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Muscle atrophy, characterized by progressive loss of muscle mass and function, is driven by muscle\u2010specific E3 ligases MAFbx and MuRF1. While transcriptional regulation of E3 ligases is documented, the mechanism of their regulation by the ubiquitin\u2013proteasome system remains unclear. This study aims to identify a deubiquitinase (DUB) regulating these E3 ligases and reveal the mechanisms underlying the mitigation of muscle atrophy through inhibition of the discovered DUB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentiated C2C12 myotubes were screened using siRNAs to identify DUB genes that can regulate muscle atrophy. Muscle fibre cross\u2010sectional area (CSA), grip strength and gene expression (MAFbx, MyoD, etc.) were evaluated in muscle atrophy\u2010induced mouse model. Human translational relevance was analysed using GTEx skeletal muscle data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified that OTU DUBs family genes are increased (log2 FC &gt;\u20091,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in DEX\u2010induced muscle atrophy. Pharmacological (ubiquitin isopeptidase inhibitor I, G5) and genetic inhibition of YOD1 alleviated DEX\u2010 and denervation\u2010induced muscle atrophy by MAFbx destabilization. The UBX domain of YOD1 was found to interact with the LZ domain of MAFbx, and YOD1 stabilized the MAFbx protein by removing polyubiquitin chains at lysine 48 in MAFbx. In in\u00a0vivo mouse models, G5 treatment effectively ameliorated DEX\u2010 or NTX\u2010induced muscle atrophy. Specifically, G5 increased grip strength by 37.64% (DEX,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and 36.37% (NTX,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while muscle fibre size was improved by 35.85% (DEX,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and 30.76% (NTX,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). These improvements were accompanied by the restoration of MyoD and eIF3\u2010f expression. Consistently, GTEx\u2010based analysis revealed that high YOD1 expression in human skeletal muscles is significantly associated with an increased proportion of smaller fibres (&lt;\u20092000\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      ), correlating with enriched proteostasis (NES\u2009=\u20091.51)\u2010related and muscle development (NES\u2009=\u2009\u22121.44)\u2010related transcriptional signatures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study indicates that YOD1 inhibition destabilizes MAFbx protein levels, leading to protection against DEX\u2010 and denervation\u2010induced muscle atrophy. Integration of human GTEx data further supports the translational relevance of YOD1 as a regulator of muscle fibre homeostasis. This study provides new insights into the post\u2010translational regulation of muscle\u2010specific E3 ligases and presents evidence showing that targeting YOD1 is a promising therapeutic approach for the prevention and treatment of muscle atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70300","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:57:41Z","timestamp":1777456661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deubiquitinase YOD1 Inhibition Suppresses DEX\u2010 and Denervation\u2010Induced Muscle Atrophy Through MAFbx Destabilization"],"prefix":"10.1002","volume":"17","author":[{"given":"Jongbeom","family":"Chae","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine Keimyung University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon\u00a0Min","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Keimyung University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u00a0Un","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Keimyung University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simmyung","family":"Yook","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon Gyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6822-5685","authenticated-orcid":false,"given":"Hyo\u00a0Je","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Chungbuk National University  Cheongju South 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Science and Technology (GIST)  Gwangju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeg\u00a0Kyu","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Keimyung University  Daegu South Korea"},{"name":"Center for Forensic Pharmaceutical Science Keimyung University  Daegu South 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