Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor
- Teruaki Nomura,
- Md Matiullah Khan,
- Sunil C. Kaul,
- Hai-Dong Dong,
- Renu Wadhwa,
- Clemencia Colmenares,
- Isao Kohno, and
- Shunsuke Ishii
- Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; National Institute of Bioscience and Human Technology, Agency of Industrial Science and Technology, Tsukuba, Ibaraki 305-0046, Japan; Chugai Research Institute for Molecular Medicine, Niihari, Ibaraki 300-4101, Japan; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195 USA; Iatron Laboratories Inc., Tako, Katori, Chiba 289-2247, Japan; CREST (Core Research for Evolutional Science and Technology), Japan Science and Technology Corporation (JST)
Abstract
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 skiproto-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 (TRβ). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRβ. Inski-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.
