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PMID:18193033

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Citation

Li, J and Wang, CY (2008) TBL1-TBLR1 and beta-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis. Nat. Cell Biol. 10:160-9

Abstract

Aberrant Wnt signalling promotes oncogenesis by increasing the nuclear accumulation of beta-catenin to activate downstream target genes. However, the mechanism of beta-catenin recruitment to the Wnt target-gene promoter, a critical step for removing the co-repressor complex, is largely unknown. Here, we report that transducin beta-like protein 1 (TBL1) and its highly related family member TBLR1 were required for Wnt-beta-catenin-mediated transcription. Wnt signalling induced the interaction between beta-catenin and TBL1-TBLR1, as well as their binding to Wnt target genes. Importantly, the recruitment of TBL1-TBLR1 and beta-catenin to Wnt target-gene promoters was mutually dependent on each other. Furthermore, the depletion of TBL1-TBLR1 significantly inhibited Wnt-beta-catenin-induced gene expression and oncogenic growth in vitro and in vivo. Our results unravel two new components required for nuclear beta-catenin function, and have important implications in developing new strategies for inhibiting Wnt-beta-catenin-mediated tumorigenesis.

Links

PubMed Online version:10.1038/ncb1684

Keywords

Cell Line; Cell Line, Tumor; Cell Transformation, Neoplastic/metabolism; Humans; Nuclear Proteins/metabolism; Promoter Regions, Genetic; Proteasome Endopeptidase Complex/metabolism; Protein Transport; Receptors, Cytoplasmic and Nuclear/metabolism; Repressor Proteins/metabolism; Signal Transduction; Transcriptional Activation/physiology; Transducin/metabolism; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt3 Protein; beta Catenin/physiology

Significance

Annotations

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

HUMAN:TBL1X

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:TBL1X

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NQB0

F

Seeded From UniProt

complete

HUMAN:TBL1X

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TBL1X

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TBL1X

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:TBL1X

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TBL1X

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:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BZK7

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60907

F

Seeded From UniProt

complete

HUMAN:CTNB1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTNB1

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

HUMAN:TBL1R

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:TBL1R

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TBL1R

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TBL1R

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:TBL1R

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TBL1R

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:TF7L2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60907

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CTNB1

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:CTNB1

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CTNB1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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