Anti-Ski-Like Oncogene (SKIL, SNO, SNOA, SNON)

Three Smad transcriptional co-repressors, namely Ski (Sloan-Kettering Institute proto-oncogene), SnoN (Ski-related novel gene, non Alu-containing), and TGIF (TG-interacting factor), have been identified (25,27-29). They exert transcriptional repression by numerous mechanisms (30-33). Clearly, Smad transcriptional co-repressors are unique regulatory components within the nuclei during the final stage of TGF-1 signaling, hence, their abundance and activity allow the cell to make the decision whether to proceed with the transcription of TGF-1-responsive genes. However, despite the obvious importance of Smad transcriptional co-repressors in controlling TGF-1 signaling, the regulation and relative significance of their expression in fibrotic kidney are completely unknown. SKI is an 80-90 kD member of the SKI family of oncoproteins. SKI is best known for inhibiting TGF-beta signaling through its association with the SMAD proteins. Human SKI is 728 aa long and contains an N-terminal Cys-rich region (aa 94-192) and a C-terminal coiled-coil oligomerization domain (aa 536-710). Over the region used as immunogen, human and mouse SKI protein sequences are 96% identical. , The Ski and Sno proteins are components of a macromolecular complex containing the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. The complex mediates repression by a number of nuclear hormone receptors and Mad, and MeCP2. In addition, Ski and Sno can render cells resistant to TGF-beta by binding to Smads. Ski (v-ski) was discovered as a viral oncogene from the genome of avian Sloan-Kettering retrovirus. Overexpression of both v-ski and cellular homolog c-ski in avian fibroblasts leads to anchorage-independent growth and morphological transformation of chicken embryo fibroblasts. Overexpression of c-ski has also been observed in several types of human cancer cells. New results show that Ski associates with Smads2, 3 and 4 proteins in response to TGF-beta stimulation. Interactions between Ski and Smad2, 3 and 4 blocks Smads-mediated transcriptional activation as well as TGF-beta-induced growth suppression of epithelial cells, suggesting oncogenic effects of Ski derive in part through its ability to antagonize the growth-inhibitory signals initiated by members of the TGF-beta family of ligands. Ski is also required for transcriptional repression mediated by Mad involved in negative regulation of cellular proliferation and plays a role in muscle differentiation.Ski (v-ski) was discovered as a viral oncogene from the genome of avian Sloan-Kettering retrovirus. Overexpression of both v-ski and cellular homolog c-ski in avian fibroblasts leads to anchorage-independent growth and morphological transformation of chicken embryo fibroblasts. Overexpression of c-ski has also been observed in several types of human cancer cells. New results show that Ski associates with Smads2, 3 and 4 proteins in response to TGF-beta stimulation. Interactions between Ski and Smad2, 3 and 4 blocks Smads-mediated transcriptional activation as well as TGF-beta-induced growth suppression of epithelial cells, suggesting oncogenic effects of Ski derive in part through its ability to antagonize the growth-inhibitory signals initiated by members of the TGF-beta family of ligands. Ski is also required for transcriptional repression mediated by Mad involved in negative regulation of cellular proliferation and plays a role in muscle differentiation. , Applications: , Suitable for use in ELISA, Western Blot, Immunohistochemistry. Other applications not tested. Recommended Dilution: Western Blot: 1:1000-1:2000, Immunohistochemistry: 2-2.5ug/ml, Optimal dilutions to be determined by the researcher. Storage and Stability: May be stored at 4°C for short-term only. For long-term storage and to avoid repeated freezing and thawing, aliquot and store at -20°C. Aliquots are stable for at least 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.,