PMID:16287852

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
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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

References

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