SKI Like Oncogene (SKIL)

The mouse Sno gene expresses 2 isoforms, SnoN and SnoN2, that are different from each other in a location downstream of the site of alternative splicing previously described in the human SNO gene. SnoN2 is missing a 138-bp coding segment present in mouse SnoN and human SNON. TGFB induces activation and nuclear translocation of SMAD2, SMAD3, and SMAD4. SMAD3 causes degradation of SnoN, allowing a SMAD2/SMAD4 complex to activate TGFB target genes. To initiate a negative feedback mechanism that permits a precise and timely regulation of TGFB signaling, TGFB also induces an increased expression of SnoN at a later stage, which in turn binds to SMAD heteromeric complexes and shuts off TGFB signaling.