Ski and SnoN: antagonistic proteins of TGF beta signaling

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 wer e Known to bind to DNA indirectly, very little was known about the mechanis m which enables these factors to induce tumorigenesis. We know now that Sno N and Ski interact with the SMAD proteins which are mediators of TGF beta s ignaling. These SMADs enable recruitment to target gene promoters of SnoN a nd Ski as well as the histone deacetylase activity which is associated with them. Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGF beta signaling deregulation of SnoN or Ski expression lea ds to total inhibition of TGF beta signaling and of the tumor suppressors S mad2 and Smad4, which can explain the role of SnoN and Ski as oncogenes.