Copyright © 2004 Cascade BioScience, Inc. All rights reserved.
Ski and SnoN are two proto-oncogenes that, at high cellular concentrations, are associated with tumors. Up to now, apart the fact that SnoN and Ski were known to bind to DNA indirectly, very little was known about the mechanism which enables these factors to induce tumorigenesis .We know now that SnoN and Ski interact with the SMAD proteins which are mediators of TGF-beta signaling. Ligand-activated SMADs recruit SnoN and Ski as well as their partner, histone deacetylase, to TGF-beta responsive promoters resulting in down regulation of the gene expression Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGF-beta signaling, deregulation of SnoN or Ski expression leads to total inhibition of TGF-beta signaling and of the tumor suppressors Smad2 and Smad 4, which can explain the role of SnoN and Ski as oncogenes.
