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J Biol Chem. 2009 Jul 31;284(31):20629-37. doi: 10.1074/jbc.M109.014332. Epub 2009 Jun 11.

Requirement of cell cycle and apoptosis regulator 1 for target gene activation by Wnt and beta-catenin and for anchorage-independent growth of human colon carcinoma cells.

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1
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90089, USA.

Abstract

Aberrant Wnt signaling promotes oncogenesis by increasing cellular levels of beta-catenin, which associates with DNA-bound transcription factors and activates Wnt target genes. However, the molecular mechanism by which beta-catenin mediates gene expression is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which was recently shown to function as a transcriptional coactivator for nuclear receptors, also interacts with beta-catenin and enhances the ability of beta-catenin to activate expression of transiently transfected reporter genes. Furthermore, association of CCAR1 with the promoter of an endogenous Wnt/beta-catenin target gene in a colon cancer cell line depends on the presence of beta-catenin. Depletion of CCAR1 inhibits expression of several Wnt/beta-catenin target genes and suppresses anchorage-independent growth of the colon cancer cell line. Thus, CCAR1 is a novel component of Wnt/beta-catenin signaling that plays an important role in transcriptional regulation by beta-catenin and that, therefore, may represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/beta-catenin signaling.

PMID:
19520846
PMCID:
PMC2742827
DOI:
10.1074/jbc.M109.014332
[Indexed for MEDLINE]
Free PMC Article
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