1MR1, 1SBX649720481ENSG00000157933ENSMUSG00000029050P12755Q60698NM_003036NM_011385NM_001357191NP_003027n/aThe SKI protein is a nuclear proto-oncogene that is associated with tumors at high cellular concentrations.
[5] SKI has been shown to interfere with normal cellular functioning by both directly impeding expression of certain genes inside the nucleus of the cell as well as disrupting signaling proteins that activate genes.
[7] This has been associated with cancer due to the large number of roles that peptide growth factors, of which TGF-beta are a subfamily, play in regulating cellular functions such as cell proliferation, apoptosis, specification, and developmental fate.
Specifically, avian fibroblasts depend on the SKI protein as a transcription co-regulator inducing transformation.
[9] The aforementioned DHD region is specifically employed for protein-protein interactions, while the 191 amino acid C terminus mediates oligomerization.
SKI also directly interacts with the R-Smad ∙ Smad-4 complex, which directly represses normal transcription of the TGF-β responsive genes, inactivating the cell's ability to stop growth and division, creating cancerous cells.
Currently it is thought that the SKI protein prevents response to TFG- β levels, causing tumor formation.