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PMID:18838381

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Citation

Lin, Z, Gao, C, Ning, Y, He, X, Wu, W and Chen, YG (2008) The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/beta-catenin signaling. J. Biol. Chem. 283:33053-8

Abstract

The canonical Wnt/beta-catenin pathway plays a pivotal role in regulating embryogenesis and tumorigenesis by promoting cell proliferation. BAMBI (BMP and activin membrane-bound inhibitor) has previously been shown to negatively regulate the signaling activity of transforming growth factor-beta, activin, and BMP and was identified as a target of beta-catenin in colorectal and hepatocellular tumor cells. In this study, we provide evidence that BAMBI can promote the transcriptional activity of Wnt/beta-catenin signaling. Overexpression of BAMBI enhances the expression of Wnt-responsive reporters, whereas knockdown of endogenous BAMBI attenuates them. Accordingly, BAMBI also promotes the nuclear translocation of beta-catenin. BAMBI interacts with Wnt receptor Frizzled5, coreceptor LRP6, and Dishevelled2 and increases the interaction between Frizzled5 and Dishevelled2. Finally we show that BAMBI promotes the expression of c-myc and cyclin D1 and increases Wnt-promoted cell cycle progression. Altogether, our data indicate that BAMBI can function as a positive regulator of the Wnt/beta-catenin pathway to promote cell proliferation.

Links

PubMed PMC2662247 Online version:10.1074/jbc.M804039200

Keywords

Active Transport, Cell Nucleus/physiology; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Cell Cycle/physiology; Cell Line, Tumor; Cell Nucleus/genetics; Cell Nucleus/metabolism; Cyclin D1/genetics; Cyclin D1/metabolism; Frizzled Receptors/genetics; Frizzled Receptors/metabolism; Humans; LDL-Receptor Related Proteins/genetics; LDL-Receptor Related Proteins/metabolism; Low Density Lipoprotein Receptor-Related Protein-6; Membrane Proteins/genetics; Membrane Proteins/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism; Proto-Oncogene Proteins c-myc/genetics; Proto-Oncogene Proteins c-myc/metabolism; Signal Transduction/physiology; Transcription, Genetic/physiology; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism; Wnt Proteins/genetics; Wnt Proteins/metabolism; beta Catenin/genetics; beta Catenin/metabolism

Significance

Annotations

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

HUMAN:BAMBI

involved_in

GO:0032092: positive regulation of protein binding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BAMBI

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BAMBI

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13467

F

Seeded From UniProt

complete

HUMAN:BAMBI

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BAMBI

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:BAMBI

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:FZD5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13145

F

Seeded From UniProt

complete


See also

References

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