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Papers In Press, published online ahead of print May 5, 2003
INSERM U482, INSERM, Hôpital St-Antoine, Paris 75571
Corresponding Author: atfi{at}pop.st-antoine.inserm.fr
The phosphorylation of Smad2 and Smad3 by the TGF-b-activated receptor kinases and their subsequent heterodimerization with Smad4 and translocation to the nucleus form the basis for a model how Smad proteins work to transmit TGF-b signals. The transcriptional activity of Smad2/Smad4 or Smad3/Smad4 complexes can be limited by the corepressor Ski, which is believed to interact with Smad complexes on TGF-b-responsive promoters and represses their ability to activate TGF-b target genes by assembling on DNA a repressor complex containing histone deacetylase. Here we show that Ski can block TGF-b signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-b type I receptor. Furthermore, we demonstrate that overexpression of Ski induces the assembly of Smad2/Smad4 and Smad3/Smad4 complexes independent of TGF-b signaling. The ability of Ski to engage Smad proteins in non-productive complexes provides new insights into the molecular mechanism used by Ski for disabling TGF-b signaling.
J. Biol. Chem, 10.1074/jbc.M304459200
Submitted on April 29, 2003
Revised on May 5, 2003
Accepted on May 5, 2003
The oncoprotein Ski acts as an antagonist of TGF-b signaling by suppressing Smad2 phosphorylation
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