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) medi ates transcriptional repression by nuclear hormone receptors and Mad. The p roteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMR T and mSin3A, and forms a complex with HDAC. c-Ski and its related gene pro duct Sno are required for transcriptional repression by Mad and thyroid hor mone receptor (TR beta). The oncogenic form, v-Ski, which lacks the mSin3A- binding domain, acts in a dominant-negative fashion, and abrogates transcri ptional repression by Mad and TR beta. 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 repres sion mediated by this complex. The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenes is.