Transcription regulator SKI/SnoN (IPR023216)

Short name: Tscrpt_reg_SKI_SnoN

Overlapping homologous superfamilies


Family relationships


This entry represents the SKI/SnoN family of proteins, which are the products of the oncogenic sno gene. This gene was identified based on its homology to v-ski, the transforming component of the Sloan-Kettering virus. Both Ski and SnoN are potent negative regulators of TGF-beta. Overexpression of Ski or SnoN results in oncogenic transformation of avian fibroblasts; however it may also result in terminal differentiation and therefore the Ski/SnoN mechanism of action is thought to be complex [PMID: 19114989].

These proteins do not have catalyitic or DNA-binding activity and therefore function primarily through interction with other proteins. Despite their lack of DNA-binding ability, their primary function is related to transcriptional regulation, in particular the negative regulation of TGF-beta signalling [PMID: 15108807]. Ski/SnoN interact concurrently with co-Smad and R-Smad and in doing so block the ability of the Smad complexes to activate transcription of the TGF-beta target genes [PMID: 12419246]. Binding of Ski/SnoN may additionally stabilise the Smad heteromer on DNA, therefore preventing further binding of active Smad complexes [PMID: 15107821]. As Smad complexes critically mediate the inhibitory signals of TGF-beta in epithelial cells, high levels of SKI/SnoN may promote cell proliferation.

High levels of SnoN have been shown to stabilise p53 with a resultant increase in premature senescence. SnoN interacts with the PML protein and is then recruited to the PML nuclear bodies, resulting in stabilisation of p53 and premature senescence [PMID: 19745809].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.