Fig. 1.

Model of regulation of atrogin by tumor necrosis factor-α (TNF). A: inhibition of protein kinase B (AKT) leads to activation of Forkhead box O transcription factor (Foxo) and an increase in atrogin mRNA. We hypothesized that TNF might increase atrogin expression by inhibiting AKT. B: we propose TNF increases atrogin expression by overriding the inhibitory effects of AKT and activating Foxo4 by an unknown mechanism. atrogin, atrogin-1/MAFbx muscle atrophy F-box; IGF, insulin-like growth factor; PI3K, phosphoinositide 3-kinase.