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, Shunsuke Ishii

Research output: Contribution to journalArticle

239 Scopus citations

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 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 (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. 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.

Original languageEnglish (US)
Pages (from-to)412-423
Number of pages12
JournalGenes and Development
Volume13
Issue number4
DOIs
StatePublished - Feb 15 1999

Keywords

  • Histone deacetylase complex
  • Mad
  • N-CoR/SMRT corepressor
  • Ski
  • mSin3

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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