FOXO1 and activated glucocorticoid receptor (NR3C1) directly activate transcription of the TRIM63 gene, acting synergistically. TRIM63 (MuRF1) is an E3 ubiquitin ligase involved in degradation of muscle proteins and muscle atrophy during starvation, similar to FBXO31 (atrogin-1) (Waddell et al. 2008).
FOXO1 and FOXO3 directly activate TRIM63 gene transcription acting synergistically with SMAD3 (Bollinger et al. 2014, Wang et al. 2017). SMAD3 in the nucleus exist as a heterotrimer composed of two molecules of SMAD2 or SMAD3 and one molecule of SMAD4.