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.
Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan.
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Nomura
M M
MM
Khan
S C
SC
Kaul
H D
HD
Dong
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Wadhwa
C
C
Colmenares
I
I
Kohno
S
S
Ishii
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056971:Nuclear Receptor Co-Repressor 1; D009955:Ornithine Decarboxylase / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic / Q000235:genetics
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499479:Mad protein, mouse; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011518:Proto-Oncogene Proteins; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C512653:Ski protein, mouse; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D009955:Ornithine Decarboxylase