Transcription of the FBXO32 gene, encoding Atrogin-1, is positively regulated by FOXO1, FOXO3 and FOXO4 (Senf et al. 2011). Direct binding to the FBXO32 gene promoter has been demonstrated for FOXO1 (Sandri et al. 2004) and FOXO3 (Raffaello et al. 2010), but not FOXO4. Atrogin-1 is a component of an SCF ubiquitin ligase complex that promotes degradation of muscle cell proteins during muscle atrophy (Tintignac et al. 2005). The ability of the Insulin-like growth factor 1 (IGF1) to prevent muscle atrophy depends on PI3K/AKT-mediated inactivation of FOXO transcription factors (Stitt et al. 2004). Acetylation of FOXO3 negatively regulates FOXO3-mediated upregulation of FBXO32 (Bertaggia et al. 2012).
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