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Gene Review

Ski  -  ski sarcoma viral oncogene homolog (avian)

Mus musculus

Synonyms: 2310012I02Rik, 2610001A11Rik, AA062172, AA589460, BC004088, ...
 
 
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Disease relevance of Ski

  • Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo [1].
  • In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass [2].
  • Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury [3].
  • Quail embryo cells (QECs) are primary cultures of fibroblastoid cells that become myogenic after infection with avian retroviruses expressing the ski oncogene (SKVs). ski also stimulates proliferation of QECs and induces morphological transformation and anchorage-independent growth [4].
 

High impact information on Ski

  • Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice [2].
  • Transgenic mice embryos expressing long ds-RNA for the transcriptional corepressor Ski from this vector exhibited phenotypes that were remarkably similar to those of Ski-deficient embryos, including defects of neural tube closure and eye formation [5].
  • Furthermore, a Ski mutation enhanced the digit abnormalities caused by the Gli3 gene mutation [6].
  • These results show that Ski is a component of the HDAC complex and that Ski is required for the transcriptional repression mediated by this complex [7].
  • The myelination-regulating transcription factor Oct6 is involved in a complex modulatory relationship with Ski [8].
 

Biological context of Ski

 

Anatomical context of Ski

 

Associations of Ski with chemical compounds

  • An association between Ski and C184M involving the leucine-rich region of C184M and the C-terminal coiled-coil motif of Ski was confirmed by glutathione S-transferase pull-down and immunoprecipitation assays [10].
  • The predictive value of these profiles was verified by demonstrating that NTDs of Ski-/- mutant mice, whose profile suggested resistance to folate supplementation, were not suppressed with dietary folate supplementation [11].
  • Defects in Ski(-)(/)(-)() mice closely resemble those described in animals lacking several of the retinoic acid receptor genes, or in animals exposed to excess retinoic acid during gestation [12].
  • The mice were divide into 3 subgroups, - one without protectans, - one protected by the sun protection lotion Sea and Ski, factor 5, - and one by Piz Buin, Factor 6 [13].
 

Physical interactions of Ski

 

Other interactions of Ski

  • c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity [15].
  • The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis [7].
  • Further more, Ski and Sno negatively regulate transforming growth factor-beta (TGF-beta) signaling by recruiting this complex to Smads [16].
  • Oncogenic activation of c-Myb correlates with a loss of negative regulation by TIF1beta and Ski [17].
  • We have shown that Ski is an important negative regulator of the Smad proteins [18].
 

Analytical, diagnostic and therapeutic context of Ski

References

  1. Activation of a muscle-specific enhancer by the Ski proto-oncogene. Engert, J.C., Servaes, S., Sutrave, P., Hughes, S.H., Rosenthal, N. Nucleic Acids Res. (1995) [Pubmed]
  2. Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice. Colmenares, C., Heilstedt, H.A., Shaffer, L.G., Schwartz, S., Berk, M., Murray, J.C., Stavnezer, E. Nat. Genet. (2002) [Pubmed]
  3. Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury. Fukasawa, H., Yamamoto, T., Togawa, A., Ohashi, N., Fujigaki, Y., Oda, T., Uchida, C., Kitagawa, K., Hattori, T., Suzuki, S., Kitagawa, M., Hishida, A. Kidney Int. (2006) [Pubmed]
  4. The ski oncogene induces muscle differentiation in quail embryo cells. Colmenares, C., Stavnezer, E. Cell (1989) [Pubmed]
  5. Generation of Ski-knockdown mice by expressing a long double-strand RNA from an RNA polymerase II promoter. Shinagawa, T., Ishii, S. Genes Dev. (2003) [Pubmed]
  6. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3. Dai, P., Shinagawa, T., Nomura, T., Harada, J., Kaul, S.C., Wadhwa, R., Khan, M.M., Akimaru, H., Sasaki, H., Colmenares, C., Ishii, S. Genes Dev. (2002) [Pubmed]
  7. Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Nomura, T., Khan, M.M., Kaul, S.C., Dong, H.D., Wadhwa, R., Colmenares, C., Kohno, I., Ishii, S. Genes Dev. (1999) [Pubmed]
  8. The protooncogene Ski controls Schwann cell proliferation and myelination. Atanasoski, S., Notterpek, L., Lee, H.Y., Castagner, F., Young, P., Ehrengruber, M.U., Meijer, D., Sommer, L., Stavnezer, E., Colmenares, C., Suter, U. Neuron (2004) [Pubmed]
  9. Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells. Wang, W., Mariani, F.V., Harland, R.M., Luo, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. The Ski-binding protein C184M negatively regulates tumor growth factor-beta signaling by sequestering the Smad proteins in the cytoplasm. Kokura, K., Kim, H., Shinagawa, T., Khan, M.M., Nomura, T., Ishii, S. J. Biol. Chem. (2003) [Pubmed]
  11. Parallel changes in metabolite and expression profiles in crooked-tail mutant and folate-reduced wild-type mice. Ernest, S., Carter, M., Shao, H., Hosack, A., Lerner, N., Colmenares, C., Rosenblatt, D.S., Pao, Y.H., Ross, M.E., Nadeau, J.H. Hum. Mol. Genet. (2006) [Pubmed]
  12. Ocular Abnormalities in Mice Lacking the Ski Proto-oncogene. McGannon, P., Miyazaki, Y., Gupta, P.C., Traboulsi, E.I., Colmenares, C. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  13. Alterations to eye structures in hairless mice by long-term ultraviolet irradiation. A histopathological study. Vangsted, P. Acta ophthalmologica. (1985) [Pubmed]
  14. DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI. Tarapore, P., Richmond, C., Zheng, G., Cohen, S.B., Kelder, B., Kopchick, J., Kruse, U., Sippel, A.E., Colmenares, C., Stavnezer, E. Nucleic Acids Res. (1997) [Pubmed]
  15. c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity. Pessah, M., Marais, J., Prunier, C., Ferrand, N., Lallemand, F., Mauviel, A., Atfi, A. J. Biol. Chem. (2002) [Pubmed]
  16. The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice. Shinagawa, T., Dong, H.D., Xu, M., Maekawa, T., Ishii, S. EMBO J. (2000) [Pubmed]
  17. Oncogenic activation of c-Myb correlates with a loss of negative regulation by TIF1beta and Ski. Nomura, T., Tanikawa, J., Akimaru, H., Kanei-Ishii, C., Ichikawa-Iwata, E., Khan, M.M., Ito, H., Ishii, S. J. Biol. Chem. (2004) [Pubmed]
  18. Negative regulation of BMP signaling by the ski oncoprotein. Luo, K. The Journal of bone and joint surgery. American volume. (2003) [Pubmed]
  19. Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues. Arndt, S., Poser, I., Schubert, T., Moser, M., Bosserhoff, A.K. Lab. Invest. (2005) [Pubmed]
 
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