Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor
Copyright policy )Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor
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.
- University of Tokyo Japan
- Cleveland Clinic United States
- Chugai Pharmaceutical Co. Japan
- National Institute of Advanced Industrial Science and Technology Japan
- RIKEN Japan
Mice, Knockout, Receptors, Thyroid Hormone, Transcription, Genetic, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Fluorescent Antibody Technique, Nuclear Proteins, Embryo, Mammalian, Ornithine Decarboxylase, Histone Deacetylases, DNA-Binding Proteins, Repressor Proteins, Mice, Sin3 Histone Deacetylase and Corepressor Complex, Gene Expression Regulation, Proto-Oncogene Proteins, Mutation, Animals, Nuclear Receptor Co-Repressor 1, In Situ Hybridization, Protein Binding
Mice, Knockout, Receptors, Thyroid Hormone, Transcription, Genetic, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Fluorescent Antibody Technique, Nuclear Proteins, Embryo, Mammalian, Ornithine Decarboxylase, Histone Deacetylases, DNA-Binding Proteins, Repressor Proteins, Mice, Sin3 Histone Deacetylase and Corepressor Complex, Gene Expression Regulation, Proto-Oncogene Proteins, Mutation, Animals, Nuclear Receptor Co-Repressor 1, In Situ Hybridization, Protein Binding
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