{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:40:52Z","timestamp":1791942052695,"version":"4.3.4"},"reference-count":56,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The Forkhead boxO (FoxO) transcription factors are activated and necessary for the muscle atrophy during several pathophysiological conditions, including muscle disuse and cancer cachexia. Yet, the mechanisms which lead to FoxO activation are not well defined. Recent data from our lab and others indicate that the activity of FoxO is repressed under basal conditions via reversible lysine acetylation, which becomes compromised during catabolic conditions. The purpose of the current study was therefore to determine the extent to which histone deacetylase (HDAC) proteins contribute to FoxO activation and induction of the muscle atrophy program. Through the use of various pharmacological inhibitors to block HDAC activity we demonstrate that class I HDACs are key regulators of FoxO and the muscle atrophy program during both nutrient deprivation and skeletal muscle disuse. Furthermore, we demonstrate through the use of WT and d.n. HDAC1 expression plasmids that HDAC1 is sufficient to activate FoxO and induce muscle fiber atrophy, in vivo, and is necessary for the muscle fiber atrophy associated with muscle disuse. The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to its induction of several atrophy genes, including atrogin-1, which required FoxO3a deacetylation. Moreover, pharmacological inhibition of class I HDACs during muscle disuse via treatment with MS-275 significantly attenuated both disuse muscle fiber atrophy and contractile dysfunction. Together these data solidify the importance of class I HDACs in the muscle atrophy program and indicate that class I HDAC inhibitors are feasible countermeasures to impede muscle atrophy and weakness.<\/jats:p>","DOI":"10.1242\/jcs.136390","type":"journal-article","created":{"date-parts":[[2014,1,25]],"date-time":"2014-01-25T02:37:59Z","timestamp":1390617479000},"source":"Crossref","is-referenced-by-count":83,"title":["HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy"],"prefix":"10.1242","author":[{"given":"Adam W.","family":"Beharry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja B.","family":"Sandesara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo F.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Senf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Judge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2021042614280032000_b1","doi-asserted-by":"publisher","first-page":"C587","DOI":"10.1152\/ajpcell.00142.2011","article-title":"Posttranslational modifications control FoxO3 activity during denervation.","volume":"302","author":"Bertaggia","year":"2012","journal-title":"Am. 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