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PMID:10811619

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Citation

Shinagawa, T, Dong, HD, Xu, M, Maekawa, T and Ishii, S (2000) The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice. EMBO J. 19:2280-91

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. Further more, Ski and Sno negatively regulate transforming growth factor-beta (TGF-beta) 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.

Links

PubMed PMC384369 Online version:10.1093/emboj/19.10.2280

Keywords

Animals; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Mice; Neoplasms, Experimental/genetics; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Signal Transduction; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SKIL

acts_upstream_of_or_within

GO:0002260: lymphocyte homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387096

P

Seeded From UniProt

complete

MOUSE:SKIL

acts_upstream_of_or_within

GO:0001825: blastocyst formation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387096

P

  • results_in_formation_of:(EMAPA:16044)

Seeded From UniProt

complete

MOUSE:SKIL

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:87951)

Seeded From UniProt

complete

MOUSE:SKIL

acts_upstream_of_or_within

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387096

P

  • occurs_in:(CL:0000084)|occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:SKIL

acts_upstream_of_or_within

GO:1902231: positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387096

P

  • regulates_o_occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:SKIL

acts_upstream_of_or_within

GO:1902043: positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387096

P

  • regulates_o_occurs_in:(CL:0000236)|regulates_o_occurs_in:(CL:0000057)

Seeded From UniProt

complete


See also

References

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