Atrogin-1, an E3 ubiquitin ligase, is increased in numerous models of muscle atrophy and is seen as a potential therapeutic target to combat muscle wasting. While previous rodent studies have consistently shown that under catabolic conditions, Atrogin-1 is regulated by FoXO transcription factors, studies in atrophic human skeletal muscle do not support a dominant role of FoXO. Our aim was to identify potential transcriptional regulators of Atrogin-1 in human and mouse myotubes. Human primary and C2C12 myotubes were infected with a c-MyC, C/EBPa or PPARd adenovirus for 48 h. Atrogin-1 mRNA levels were increased by 72% and decreased by 52% with PPARd and C/EBPa over-expression, respectively. mRNA analysis in human myotubes is in progress. At the protein level there was a 74% and 46% increase in Atrogin-1 with C/EBPa over-expression in mouse and human myotubes, respectively. c-MyC and PPARd over-expression increased Atrogin-1 protein by 46% and 62% in mouse myotubes respectively, while in human myotubes infection with c-MyC and PPARd decreased Atrogin-1 protein levels by 23% and 26% respectively. These preliminary results suggest that Atrogin-1 may be transcriptionally regulated by factors other than FoXO, and further highlight that Atrogin-1 regulation is species dependent. Future studies will determine direct transcriptional regulators of Atrogin-1 via luciferase assays.