Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism

UBR5 is an E3 ubiquitin ligase positively associated with anabolism, hypertrophy, and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role the regulation of muscle mass remain unknown. present study aimed to elucidate these by silencing gene vivo. To achieve this aim, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior investigate impact reduced on anabolic signaling MEK/ERK/p90RSK Akt/GSK3?/p70S6K/4E-BP1/rpS6 pathways. Seven days after RNAi electroporation, although reductions overall were not detected, mean cross-sectional area (CSA) green fluorescent protein (GFP)-positive fibers (?9.5%) number large lower versus control. Importantly, significantly total RNA, synthesis, ERK1/2, Akt, GSK3? activity. Although p90RSK phosphorylation increased, levels demonstrated 45% reduction UBR5-RNAi. Finally, early events 7 knockdown culminated significant (?4.6%) larger fiber CSA (?18.5%) 30 days. This was increased phosphatase PP2Ac inappropriate chronic elevation p70S6K rpS6 between days, as well corresponding eIF4e. demonstrates that plays important anabolism/hypertrophy, whereby culminates atrophy.