SnoA Background Information The Ski family of oncogenes includes Ski and Sno (Ski-related novel gene, or Ski-like). Three isoforms of human Sno (SnoN,SnoA and SnoI) and 2 isoforms in mouse (SnoN and SnoN2, also designated sno-dE3) are produced by alternative splicing of the SKIL gene. Ski family members are nuclear proteins that form homodimers and heterodimers, bind to DNA and function as transcriptional activators and repressors. These proteins consist of five tandem repeats in the C-terminal domain and two leucine zipper motifs that are responsible for efficient DNA binding, trimerization and cellular transformation. The Ski proteins regulate TGFß induced gene-specific transcriptional activation by effectively repressing Smad activity and, thereby, inhibit TGFß induced cell growth and extracellular matrix production. The amino terminus of Ski and SnoN preferentially associates with the MH2 domain of Smad2 and Smad4 of the Smad family of transcription factors, where they then recruit the transcriptional co-repressor protein N-CoR to the complex to inhibit transcription. Alternatively, Ski proteins are negatively regulated by various Smad proteins, as TGFß induces Smad3 accumulation in the nucleus, where it is then responsible for inducing the rapid degradation of SnoN and faciliating TGFß signaling pathways and Smad-activated gene transcription.
