Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism.
As a member of the TGF-beta superfamily, myostatin is a specific negative regulator of skeletal muscle mass. To identify the downstream components in the myostatin signal transduction pathway, we used a luciferase reporter assay to elucidate myostatin-induced activity. The myostatin-induced transcription requires the participation of regulatory Smads (Smad2/3) and Co-Smads (Smad4). Conversely, inhibitory Smad7, but not Smad6, dramatically reduces the myostatin-induced transcription. This Smad7 inhibition is enhanced by co-expression of Smurf1. We have also shown that Smad7 expression is stimulated by myostatin via the interaction between Smad2, Smad3, Smad4 and the SBE (Smad binding element) in the Smad7 promoter. These results suggest that the myostatin signal transduction pathway is regulated by Smad7 through a negative feedback mechanism.
Zhu
Xiangyang
X
MetaMorphix Inc., 8510A Corridor Road, Savage, MD 20763, USA. xzhu@metamorphixinc.com
Topouzis
Stavros
S
Liang
Li-Fang
LF
Stotish
Ronald L
RL
D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D055435:Myostatin; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C525911:MSTN protein, human; D055435:Myostatin; D016212:Transforming Growth Factor beta; D004247:DNA; D008156:Luciferases