Interaction with Smad4 is indispensable for suppression of BMP signaling by c-Ski.

c-Ski is a transcriptional corepressor that interacts strongly with Smad2, Smad3, and Smad4 but only weakly with Smad1 and Smad5. Through binding to Smad proteins, c-Ski suppresses signaling of transforming growth factor-beta (TGF-beta) as well as bone morphogenetic proteins (BMPs). In the present study, we found that a mutant of ...
c-Ski, termed c-Ski (ARPG) inhibited TGF-beta/activin signaling but not BMP signaling. Selectivity was confirmed in luciferase reporter assays and by determination of cellular responses in mammalian cells (BMP-induced osteoblastic differentiation of C2C12 cells and TGF-beta-induced epithelial-to-mesenchymal transdifferentiation of NMuMG cells) and Xenopus embryos. The ARPG mutant recruited histone deacetylases 1 (HDAC1) to the Smad3-Smad4 complex but not to the Smad1/5-Smad4 complex. c-Ski (ARPG) was unable to interact with Smad4, and the selective loss of suppression of BMP signaling by c-Ski (ARPG) was attributed to the lack of Smad4 binding. We also found that c-Ski interacted with Smad3 or Smad4 without disrupting Smad3-Smad4 heteromer formation. c-Ski (ARPG) would be useful for selectively suppressing TGF-beta/activin signaling.
Mesh Terms:
Animals, Bone Morphogenetic Proteins, COS Cells, Cell Differentiation, Cells, Cultured, Cercopithecus aethiops, DNA-Binding Proteins, Embryo, Nonmammalian, Histone Deacetylases, Humans, Mutation, Osteoblasts, Protein Binding, Proto-Oncogene Proteins, Signal Transduction, Smad Proteins, Smad1 Protein, Smad4 Protein, Trans-Activators, Transforming Growth Factor beta, Xenopus, Xenopus Proteins
Mol. Biol. Cell
Date: Mar. 01, 2004
Download Curated Data For This Publication
Switch View:
  • Interactions 10