|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2007-1-29
|
|
pubmed:abstractText |
Beta-catenin is implicated in quite different cellular processes, which require a fine-tuned regulation of its function. Here we demonstrate that cyclin-dependent kinase 6 (CDK6), in association with cyclin D1 (CCND1), directly binds to beta-catenin. We showed that CCND1-CDK6 phosphorylates beta-catenin on serine 45 (S45). This phosphorylation creates a priming site for glycogen synthase kinase 3beta (GSK3beta) and is both necessary and sufficient to initiate the beta-catenin phosphorylation-degradation cascade. Moreover, co-immunoprecipitation assays using Wnt3a-conditioned medium reveals that while Wnt stimulation leads to the dissociation of beta-catenin from axin and casein kinase Ialpha (CKIalpha), Wnt treatment promotes an increase in CCND1 level and the association of beta-catenin with CCND1-CDK6. Furthermore, Wnt3a-stimulated cytosolic beta-catenin levels were higher in CDK6 knockout mouse embryonic fibroblasts (CDK6-/- MEFs) compared to wild-type MEFs. Thus, the CCND1-CDK6 complex is like to negatively regulate Wnt signaling by mediating beta-catenin phosphorylation and its subsequent degradation in Wnt-stimulated cells.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0171-9335
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
86
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
111-23
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:17208333-Animals,
pubmed-meshheading:17208333-Cattle,
pubmed-meshheading:17208333-Cells, Cultured,
pubmed-meshheading:17208333-Cyclin D1,
pubmed-meshheading:17208333-Cyclin-Dependent Kinase 6,
pubmed-meshheading:17208333-Fibroblasts,
pubmed-meshheading:17208333-Humans,
pubmed-meshheading:17208333-Mice,
pubmed-meshheading:17208333-Mice, Knockout,
pubmed-meshheading:17208333-Phosphoproteins,
pubmed-meshheading:17208333-Phosphorylation,
pubmed-meshheading:17208333-Protein Binding,
pubmed-meshheading:17208333-Protein Kinases,
pubmed-meshheading:17208333-Serine,
pubmed-meshheading:17208333-TCF Transcription Factors,
pubmed-meshheading:17208333-Trans-Activators,
pubmed-meshheading:17208333-Transcription, Genetic,
pubmed-meshheading:17208333-Wnt Proteins,
pubmed-meshheading:17208333-beta Catenin
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Modulation of beta-catenin by cyclin-dependent kinase 6 in Wnt-stimulated cells.
|
|
pubmed:affiliation |
Department of Life Science and Molecular Disease Research Center, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Korea.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
