Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2006-11-20
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2239-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
CK2 controls the recruitment of Wnt regulators to target genes in vivo.
pubmed:affiliation
Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural