Source:http://linkedlifedata.com/resource/pubmed/id/17113388
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2006-11-20
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pubmed:abstractText |
Nuclear beta-catenin is a transcriptional coactivator of LEF-1/TCF DNA-binding proteins in the Wnt/Wg signaling pathway. Casein Kinase 2 (CK2), a positive regulator of Wnt signaling, is present in beta-catenin complexes and activated in Wnt-signaling cells. We show here that CK2 enhances beta-catenin:LEF-1 transactivation in vivo and in vitro and that beta-catenin and CK2 cycle on and off the DNA in an alternating manner with the TLE1 corepressor at Wnt target genes. Interestingly, CK2 phosphorylates hLEF-1 directly and stimulates binding and transactivation of beta-catenin:LEF-1 complexes on chromatin templates in vitro. In vitro, CK2 phosphorylation of hLEF-1 strongly enhances its affinity for beta-catenin and reduces its affinity for TLE1. MALDI-TOF mass spectrometry (MS) identified two CK2 phosphorylation sites (S42, S61) within the amino terminus of hLEF-1, and mutation of these sites reduced binding to beta-catenin in vitro and transactivation in vivo. Remarkably, treatment of cells with TBB, a pharmaceutical inhibitor of CK2, blocked the recruitment and cycling of beta-catenin and TLE1 at Wnt target genes in vivo. Taken together, these data indicate that CK2 is required for the assembly and cycling of Wnt-enhancer complexes in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0960-9822
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2239-44
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17113388-Animals,
pubmed-meshheading:17113388-Casein Kinase II,
pubmed-meshheading:17113388-Cell Line, Tumor,
pubmed-meshheading:17113388-Chromatin Immunoprecipitation,
pubmed-meshheading:17113388-DNA,
pubmed-meshheading:17113388-Humans,
pubmed-meshheading:17113388-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:17113388-Mice,
pubmed-meshheading:17113388-Phosphorylation,
pubmed-meshheading:17113388-RNA Interference,
pubmed-meshheading:17113388-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17113388-Signal Transduction,
pubmed-meshheading:17113388-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:17113388-Wnt Proteins,
pubmed-meshheading:17113388-beta Catenin
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pubmed:year |
2006
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pubmed:articleTitle |
CK2 controls the recruitment of Wnt regulators to target genes in vivo.
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pubmed:affiliation |
Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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