The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation.

The phosphorylation of Smad2 and Smad3 by the transforming growth factor (TGF)-beta-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-beta 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-beta-responsive promoters and represses their ability to activate TGF-beta target genes by assembling on DNA a repressor complex containing histone deacetylase. Here we show that Ski can block TGF-beta signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-beta type I receptor. Furthermore, we demonstrate that overexpression of Ski induces the assembly of Smad2-Smad4 and Smad3-Smad4 complexes independent of TGF-beta signaling. The ability of Ski to engage Smad proteins in nonproductive complexes provides new insights into the molecular mechanism used by Ski for disabling TGF-beta signaling.
Mesh Terms:
Active Transport, Cell Nucleus, Animals, COS Cells, Cytoplasm, DNA, DNA-Binding Proteins, Dimerization, Immunoblotting, Ligands, Microscopy, Fluorescence, Phosphorylation, Plasmids, Precipitin Tests, Protein Transport, Proto-Oncogene Proteins, Signal Transduction, Smad2 Protein, Smad3 Protein, Trans-Activators, Transfection, Transforming Growth Factor beta
J. Biol. Chem.
Date: Jul. 11, 2003
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