Linked Life Data

21478268

Source:http://linkedlifedata.com/resource/pubmed/id/21478268

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-17
pubmed:abstractText
Aberrant activation of Wnt/?-catenin signaling, resulting in the expression of Wnt-regulated oncogenes, is recognized as a critical factor in the etiology of colorectal cancer. Occupancy of ?-catenin at promoters of Wnt target genes drives transcription, but the mechanism of ?-catenin action remains poorly understood. Here, we show that CARM1 (coactivator-associated arginine methyltransferase 1) interacts with ?-catenin and positively modulates ?-catenin-mediated gene expression. In colorectal cancer cells with constitutively high Wnt/?-catenin activity, depletion of CARM1 inhibits expression of endogenous Wnt/?-catenin target genes and suppresses clonal survival and anchorage-independent growth. We also identified a colorectal cancer cell line (RKO) with a low basal level of ?-catenin, which is dramatically elevated by treatment with Wnt3a. Wnt3a also increased the expression of a subset of endogenous Wnt target genes, and CARM1 was required for the Wnt-induced expression of these target genes and the accompanying dimethylation of arginine 17 of histone H3. Depletion of ?-catenin from RKO cells diminished the Wnt-induced occupancy of CARM1 on a Wnt target gene, indicating that CARM1 is recruited to Wnt target genes through its interaction with ?-catenin and contributes to transcriptional activation by mediating events (including histone H3 methylation) that are downstream from the actions of ?-catenin. Therefore, CARM1 is an important positive modulator of Wnt/?-catenin transcription and neoplastic transformation, and may thereby represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/?-catenin signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1557-3125
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
660-70
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A coactivator role of CARM1 in the dysregulation of ?-catenin activity in colorectal cancer cell growth and gene expression.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural