The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice

Toshie Shinagawa, Hai Dong Dong, Ming Xu, Toshio Maekawa, Shunsuke Ishii

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

The Ski and Sno oncoproteins are components of a macromolecular complex containing the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. This complex has been implicated in the transcriptional repression exerted by a number of repressors including nuclear hormone receptors and Mad. Furthermore, Ski and Sno negatively regulate transforming growth factor-β (TGF-β) signaling by recruiting this complex to Smads. Here we show that loss of one copy of sno increases susceptibility to tumorigenesis in mice. Mice lacking sno died at an early stage of embryogenesis, and sno was required for blastocyst formation. Heterozygous (sno(+/-)) mice developed spontaneous lymphomas at a low frequency and showed an increased level of tumor formation relative to wild-type mice when challenged with a chemical carcinogen. sno(+/-) embryonic fibroblasts had an increased proliferative capacity and the introduction of activated Ki-ras into these cells resulted in neoplastic transformation. The B cells, T cells and embryonic fibroblasts of sno(+/-) mice had a decreased sensitivity to apoptosis or cell cycle arrest. These findings demonstrate that sno acts as a tumor suppressor at least in some types of cells.

Original languageEnglish (US)
Pages (from-to)2280-2291
Number of pages12
JournalEMBO Journal
Volume19
Issue number10
DOIs
StatePublished - May 15 2000

Keywords

  • Histone deacetylase
  • Mad
  • Rb
  • Sno
  • Tumor suppressor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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