Identification of ubiquitin ligases required for skeletal muscle atrophy.
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 or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.
Bodine
S C
SC
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591-6707, USA.
Latres
E
E
Baumhueter
S
S
Lai
V K
VK
Nunez
L
L
Clarke
B A
BA
Poueymirou
W T
WT
Panaro
F J
FJ
Na
E
E
Dharmarajan
K
K
Pan
Z Q
ZQ
Valenzuela
D M
DM
DeChiara
T M
TM
Stitt
T N
TN
Yancopoulos
G D
GD
Glass
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003402:Creatine Kinase / Q000235:genetics; D052283:Creatine Kinase, MM Form; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D020869:Gene Expression Profiling; D019417:Hindlimb Suspension; D006801:Humans; D007103:Immobilization; D007527:Isoenzymes / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009121:Muscle Denervation; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics; D010453:Peptide Synthases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases; D015534:Trans-Activators; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D007527:Isoenzymes; C497417:MYF5 protein, human; C503799:MYOG protein, human; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; C503803:Myog protein, rat; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D012333:RNA, Messenger; D015534:Trans-Activators; D044843:SKP Cullin F-Box Protein Ligases; D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form; D010453:Peptide Synthases