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PMID:10049357

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Citation

Nomura, T, Khan, MM, Kaul, SC, Dong, HD, Wadhwa, R, Colmenares, C, Kohno, I and Ishii, S (1999) Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev. 13:412-23

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 (TRbeta). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRbeta. 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.

Links

PubMed PMC316468

Keywords

Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; DNA-Binding Proteins/genetics; Embryo, Mammalian/metabolism; Fluorescent Antibody Technique; Gene Expression Regulation/genetics; Histone Deacetylases/genetics; In Situ Hybridization; Mice; Mice, Knockout; Mutation/genetics; Nuclear Proteins/genetics; Nuclear Receptor Co-Repressor 1; Ornithine Decarboxylase/genetics; Protein Binding/genetics; Proto-Oncogene Proteins/genetics; Receptors, Thyroid Hormone/genetics; Repressor Proteins/genetics; Transcription, Genetic/genetics

Significance

Annotations

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

HUMAN:NCOR1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12755

F

Seeded From UniProt

complete

HUMAN:SKI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75376

F

Seeded From UniProt

complete

HUMAN:SKI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60974

F

Seeded From UniProt

complete

HUMAN:SKI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96ST3

F

Seeded From UniProt

complete

HUMAN:SKIL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60974

F

Seeded From UniProt

complete

MOUSE:SKI

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SKI

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SKI

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

Seeded From UniProt

complete

MOUSE:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q60698

F

Seeded From UniProt

complete

MOUSE:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12755

F

Seeded From UniProt

complete

MOUSE:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12757

F

Seeded From UniProt

complete

MOUSE:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12757-1

F

Seeded From UniProt

complete

HUMAN:SIN3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12755

F

Seeded From UniProt

complete


See also

References

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