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PMID:16287852

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Citation

Oswald, F, Winkler, M, Cao, Y, Astrahantseff, K, Bourteele, S, Knöchel, W and Borggrefe, T (2005) RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol. Cell. Biol. 25:10379-90

Abstract

Notch is a transmembrane receptor that determines cell fates and pattern formation in all animal species. After ligand binding, proteolytic cleavage steps occur and the intracellular part of Notch translocates to the nucleus, where it targets the DNA-binding protein RBP-Jkappa/CBF1. In the absence of Notch, RBP-Jkappa represses Notch target genes through the recruitment of a corepressor complex. We and others have identified SHARP as a component of this complex. Here, we functionally demonstrate that the SHARP repression domain is necessary and sufficient to repress transcription and that the absence of this domain causes a dominant negative Notch-like phenotype. We identify the CtIP and CtBP corepressors as novel components of the human RBP-Jkappa/SHARP-corepressor complex and show that CtIP binds directly to the SHARP repression domain. Functionally, CtIP and CtBP augment SHARP-mediated repression. Transcriptional repression of the Notch target gene Hey1 is abolished in CtBP-deficient cells or after the functional knockout of CtBP. Furthermore, the endogenous Hey1 promoter is derepressed in CtBP-deficient cells. We propose that a corepressor complex containing CtIP/CtBP facilitates RBP-Jkappa/SHARP-mediated repression of Notch target genes.

Links

PubMed PMC1291242 Online version:10.1128/MCB.25.23.10379-10390.2005

Keywords

Alcohol Oxidoreductases; Animals; Basic Helix-Loop-Helix Transcription Factors/chemistry; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryo, Nonmammalian/embryology; Embryo, Nonmammalian/metabolism; Gene Silencing; Humans; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism; Mice; Multiprotein Complexes/chemistry; Multiprotein Complexes/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism; Receptors, Notch/genetics; Receptors, Notch/metabolism; Repressor Proteins/genetics; Repressor Proteins/metabolism; Xenopus laevis/embryology; Xenopus laevis/genetics; Xenopus laevis/metabolism

Significance

Annotations

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

MOUSE:SUH

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUH

enables

GO:0001103: RNA polymerase II repressing transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96T58

F

Seeded From UniProt

complete

HUMAN:CTBP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q99708

F

Seeded From UniProt

complete

HUMAN:CTBP1

part_of

GO:0017053: transcription repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTBP1

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MINT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q99708

F

Seeded From UniProt

complete

HUMAN:MINT

involved_in

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

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MINT

part_of

GO:0017053: transcription repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MINT

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MINT

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q06330

F

Seeded From UniProt

complete

HUMAN:MINT

involved_in

GO:0050769: positive regulation of neurogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CTIP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13363

F

Seeded From UniProt

complete

HUMAN:CTIP

part_of

GO:0017053: transcription repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:COM1

enables

GO:0001103: RNA polymerase II repressing transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96T58

F

Seeded From UniProt

complete

HUMAN:COM1

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:COM1

part_of

GO:0017053: transcriptional repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTIP

part_of

GO:0017053: transcriptional repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTIP

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CTIP

enables

GO:0001103: RNA polymerase II repressing transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96T58

F

Seeded From UniProt

complete


See also

References

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