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Nomura, T, Khan, MM, Kaul, SC, Dong, HD, Wadhwa, R, Colmenares, C, Kohno, I and Ishii, S (1999) Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev. 13:412-23
The N-CoR/SMRT complex containing mSin3 and histone deacetylase (HDAC) mediates transcriptional repression by nuclear hormone receptors and Mad. The proteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMRT and mSin3A, and forms a complex with HDAC. c-Ski and its related gene product Sno are required for transcriptional repression by Mad and thyroid hormone receptor (TRbeta). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRbeta. In ski-deficient mouse embryos, the ornithine decarboxylase gene, whose expression is normally repressed by Mad-Max, is expressed ectopically. 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. The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis.
Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; DNA-Binding Proteins/genetics; Embryo, Mammalian/metabolism; Fluorescent Antibody Technique; Gene Expression Regulation/genetics; Histone Deacetylases/genetics; In Situ Hybridization; Mice; Mice, Knockout; Mutation/genetics; Nuclear Proteins/genetics; Nuclear Receptor Co-Repressor 1; Ornithine Decarboxylase/genetics; Protein Binding/genetics; Proto-Oncogene Proteins/genetics; Receptors, Thyroid Hormone/genetics; Repressor Proteins/genetics; Transcription, Genetic/genetics