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Although FOXOs are clearly essential for the induction of muscle atrophy, it is unclear whether there are other factors involved in the FOXO\u2010mediated transcriptional regulation. As such, we identified FOXO\u2013CCAAT\/enhancer\u2010binding protein \u03b4 (C\/EBP\u03b4) signaling pathway as a novel proteolytic pathway. By comparing the gene expression profiles of FOXO1\u2010transgenic (gain\u2010of\u2010function model) and FOXO1,3a,4\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    (loss\u2010of\u2010function model) mice, we identified several novel FOXO1\u2010target genes in skeletal muscle including Redd1, Sestrin1, Castor2, Chac1, Depp1, Lat3, as well as C\/EBP\u03b4. During starvation, C\/EBP\u03b4 abundance was increased in a FOXOs\u2010dependent manner. Notably, knockdown of C\/EBP\u03b4 prevented the induction of the ubiquitin\u2013proteasome system and decrease of myofibers in FOXO1\u2010activated myotubes. Conversely, C\/EBP\u03b4 overexpression in primary myotubes induced myotube atrophy. Furthermore, we demonstrated that FOXO1 enhances the promoter activity of target genes in cooperation with C\/EBP\u03b4 and ATF4. This research comprehensively identifies novel FOXO1 target genes in skeletal muscle and clarifies the pathophysiological role of FOXO1, a master regulator of skeletal muscle atrophy.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101385rr","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T10:30:16Z","timestamp":1642761016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["FOXO1 cooperates with C\/EBP\u03b4 and ATF4 to regulate skeletal muscle atrophy transcriptional program during fasting"],"prefix":"10.1096","volume":"36","author":[{"given":"Mamoru","family":"Oyabu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Nutrition Graduate School of Life and Environmental Sciences Kyoto Prefectural University  Kyoto 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