{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:21:18Z","timestamp":1759969278337,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020MH278"],"award-info":[{"award-number":["ZR2020MH278"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are complex, involving protein synthesis\/degradation imbalance. Dual\u2010specificity tyrosine phosphorylation\u2010regulated kinase 1A (DYRK1A) and ubiquitin\u2010specific peptidase 7 (USP7) have diverse cellular roles, but their coordinated function in skeletal muscle homeostasis remains poorly understood. DYRK1A overexpression in\u00a0vivo induced muscle atrophy phenotypes, including reduced muscle mass, grip strength, fiber cross\u2010sectional area (CSA), altered fiber type composition, and neuromuscular junction integrity, accompanied by elevated atrophy markers: muscle atrophy F\u2010box protein (Atrogin\u20101), muscle ring finger 1 (MuRF\u20101), myostatin and suppressed myogenic markers: myoblast determination protein 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (Mef2c), myogenic factor 5 (Myf5). Conversely, pharmacological inhibition of DYRK1A with Harmine ameliorated these atrophy phenotypes in transgenic DYRK1A overexpressing (TgD) mice. In\u00a0vivo, USP7 deficiency resulted in similar muscle wasting phenotypes. In\u00a0vitro, DYRK1A overexpression or USP7 overexpression inhibited C2C12 myoblast proliferation and differentiation, effects rescued by Wnt3a treatment or USP7 knockdown, respectively. Mechanistically, DYRK1A activity suppressed active \u03b2\u2010catenin levels. USP7 was found to interact with and deubiquitinate axis inhibition protein 1 (Axin1), leading to its stabilization. Knockdown of USP7 increased Axin1 ubiquitination and degradation, thereby promoting \u03b2\u2010catenin signaling and myogenesis, counteracting the effects of DYRK1A. Our findings reveal a novel signaling axis where DYRK1A and USP7 cooperatively suppress Wnt\/\u03b2\u2010catenin signaling to promote muscle wasting. DYRK1A likely acts upstream, potentially phosphorylating pathway components, whereas USP7 stabilizes the \u03b2\u2010catenin destruction complex scaffold protein Axin1 through deubiquitination. This coordinated action inhibits myogenesis and activates atrophy pathways. Targeting DYRK1A or USP7 could represent promising therapeutic strategies for muscle wasting disorders.<\/jats:p>","DOI":"10.1002\/iub.70061","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:46:52Z","timestamp":1758282412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DYRK1A<\/scp> Overexpression Drives Muscle Wasting by Impeding Myogenesis via a <scp>USP7<\/scp>\u2010Axin1\u2010\u03b2\u2010Catenin Regulatory Axis in Mice"],"prefix":"10.1002","volume":"77","author":[{"given":"Mei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine &amp; Laboratory of Gerontology and Anti\u2010Aging Research Qilu Hospital of Shandong University  Jinan Shandong P. R. 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