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PMID:21399610

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Citation

Benchabane, H, Xin, N, Tian, A, Hafler, BP, Nguyen, K, Ahmed, A and Ahmed, Y (2011) Jerky/Earthbound facilitates cell-specific Wnt/Wingless signalling by modulating β-catenin-TCF activity. EMBO J. 30:1444-58

Abstract

Wnt/Wingless signal transduction directs fundamental developmental processes, and upon hyperactivation triggers colorectal adenoma/carcinoma formation. Responses to Wnt stimulation are cell specific and diverse; yet, how cell context modulates Wnt signalling outcome remains obscure. In a Drosophila genetic screen for components that promote Wingless signalling, we identified Earthbound 1 (Ebd1), a novel member in a protein family containing Centromere Binding Protein B (CENPB)-type DNA binding domains. Ebd1 is expressed in only a subset of Wingless responsive cell types, and is required for only a limited number of Wingless-dependent processes. In addition, Ebd1 shares sequence similarity and can be functionally replaced with the human CENPB domain protein Jerky, previously implicated in juvenile myoclonic epilepsy development. Both Jerky and Ebd1 interact directly with the Wnt/Wingless pathway transcriptional co-activators β-catenin/Armadillo and T-cell factor (TCF). In colon carcinoma cells, Jerky facilitates Wnt signalling by promoting association of β-catenin with TCF and recruitment of β-catenin to chromatin. These findings indicate that tissue-restricted transcriptional co-activators facilitate cell-specific Wnt/Wingless signalling responses by modulating β-catenin-TCF activity.

Links

PubMed PMC3102276 Online version:10.1038/emboj.2011.67

Keywords

Animals; Blotting, Western; Cells, Cultured; Centromere Protein B/genetics; Centromere Protein B/metabolism; Colonic Neoplasms/genetics; Colonic Neoplasms/metabolism; Drosophila/genetics; Drosophila/growth & development; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Humans; Immunoenzyme Techniques; Immunoprecipitation; Kidney/cytology; Kidney/metabolism; Luciferases/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Binding; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; TCF Transcription Factors/genetics; TCF Transcription Factors/metabolism; Trans-Activators/genetics; Trans-Activators/metabolism; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt1 Protein/genetics; Wnt1 Protein/metabolism; beta Catenin/genetics; beta Catenin/metabolism

Significance

Annotations

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

HUMAN:BCL9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BRQ0

F

Seeded From UniProt

complete

HUMAN:JERKY

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:JERKY

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P27782

F

Seeded From UniProt

complete

HUMAN:JERKY

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

DROME:ARM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9W0N9

F

Seeded From UniProt

complete

MOUSE:LEF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75564

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75564

F

Seeded From UniProt

complete

DROME:PANG1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9W0N9

F

Seeded From UniProt

complete

HUMAN:PYGO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00512

F

Seeded From UniProt

complete

MOUSE:PYGO1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9W0N9

F

Seeded From UniProt

complete

DROME:Q9VP44

involved_in

GO:0007527: adult somatic muscle development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W0N9

involved_in

GO:0007527: adult somatic muscle development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W0N9

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

DROME:Q9W0N9

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9W0N9

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0039907

P

Seeded From UniProt

complete

DROME:Q9W0N9

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0015589

P

Seeded From UniProt

complete

DROME:Q9W0N9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P18824

F

Seeded From UniProt

complete

DROME:Q9W0N9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P91943

F

Seeded From UniProt

complete

DROME:Q9W0N9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9D0P5

F

Seeded From UniProt

complete


See also

References

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