|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
1999-4-22
|
|
pubmed:abstractText |
Defects in beta-catenin regulation contribute to the neoplastic transformation of mammalian cells. Dysregulation of beta-catenin can result from missense mutations that affect critical sites of phosphorylation by glycogen synthase kinase 3beta (GSK3beta). Given that phosphorylation can regulate targeted degradation of beta-catenin by the proteasome, beta-catenin might interact with an E3 ubiquitin ligase complex containing an F-box protein, as is the case for certain cell cycle regulators. Accordingly, disruption of the Drosophila F-box protein Slimb upregulates the beta-catenin homolog Armadillo. We reasoned that the human homologs of Slimb - beta-TrCP and its isoform beta-TrCP2 (KIAA0696) - might interact with beta-catenin. We found that the binding of beta-TrCP to beta-catenin was direct and dependent upon the WD40 repeat sequences in beta-TrCP and on phosphorylation of the GSK3beta sites in beta-catenin. Endogenous beta-catenin and beta-TrCP could be coimmunoprecipitated from mammalian cells. Overexpression of wild-type beta-TrCP in mammalian cells promoted the downregulation of beta-catenin, whereas overexpression of a dominant-negative deletion mutant upregulated beta-catenin protein levels and activated signaling dependent on the transcription factor Tcf. In contrast, beta-TrCP2 did not associate with beta-catenin. We conclude that beta-TrCP is a component of an E3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BTRC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBXW11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Transducin Repeat-Containing...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0960-9822
|
|
pubmed:author |
pubmed-author:AlbertII,
pubmed-author:BenarousRR,
pubmed-author:ConcordetJ PJP,
pubmed-author:DurandHH,
pubmed-author:HartMM,
pubmed-author:LassotII,
pubmed-author:MargottinFF,
pubmed-author:PerretCC,
pubmed-author:PolakisPP,
pubmed-author:RubinfeldBB,
pubmed-author:del los SantosRR
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
25
|
|
pubmed:volume |
9
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
207-10
|
|
pubmed:dateRevised |
2007-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:10074433-Animals,
pubmed-meshheading:10074433-Cadherins,
pubmed-meshheading:10074433-Carrier Proteins,
pubmed-meshheading:10074433-Cell Line,
pubmed-meshheading:10074433-Cytoskeletal Proteins,
pubmed-meshheading:10074433-Drosophila,
pubmed-meshheading:10074433-GTP-Binding Proteins,
pubmed-meshheading:10074433-Genes, Reporter,
pubmed-meshheading:10074433-HeLa Cells,
pubmed-meshheading:10074433-Humans,
pubmed-meshheading:10074433-Phosphorylation,
pubmed-meshheading:10074433-Protein Isoforms,
pubmed-meshheading:10074433-Recombinant Proteins,
pubmed-meshheading:10074433-Repetitive Sequences, Amino Acid,
pubmed-meshheading:10074433-Trans-Activators,
pubmed-meshheading:10074433-Transfection,
pubmed-meshheading:10074433-Ubiquitin-Protein Ligases,
pubmed-meshheading:10074433-beta Catenin,
pubmed-meshheading:10074433-beta-Transducin Repeat-Containing Proteins
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.
|
|
pubmed:affiliation |
Onyx Pharmaceuticals 3031 Research Drive Richmond California 94806 USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
