Figure 1.

Overview of proteasome-dependent protein degradation via the muscle-specific E3 ligase MuRF1 as induced in various wasting illness, with recognized pharmacological inhibitors also presented. The most important proteolytic pathway to mediate muscle atrophy is the ATP-dependent ubiquitin-proteasome system, whereby structural and regulatory proteins are degraded by the 26S proteasome following polyubiquitination that involves activation of E1, E2, and E3 enzymes. MuRF1 (an E3 ligase) plays a fundamental role in tagging proteins with ubiquitin during catabolic conditions, which is activated by various stimuli and signaling pathways that include NFκB and FoxO. A selection of reported pharmacological inhibitors of MuRF1-dependent muscle atrophy are presented along with the study reference. Solid lines indicate a direct effect on the target, while dotted lines indicate a secondary indirect effect. See the main text for full details.