Identification of ubiquitin ligases required for skeletal muscle atrophy

SC Bodine, E Latres, S Baumhueter, VKM Lai, L Nunez… - Science, 2001 - science.org
SC Bodine, E Latres, S Baumhueter, VKM Lai, L Nunez, BA Clarke, WT Poueymirou…
Science, 2001science.org
Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify
candidate molecular mediators of muscle atrophy, we performed transcript profiling.
Although many genes were up-regulated in a single rat model of atrophy, only a small
subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases:
Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx),
the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of …
Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box(MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.
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