Linked Life Data

16288032

Source:http://linkedlifedata.com/resource/pubmed/id/16288032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2005-11-18
pubmed:abstractText
Dysregulation of beta-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with beta-catenin. However, the functional significance of the MUC1-beta-catenin interaction is not known. Here, we show that MUC1 increases beta-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3beta (GSK3beta) phosphorylates beta-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of beta-catenin levels, our results show that MUC1 blocks GSK3beta-mediated phosphorylation and degradation of beta-catenin. To further define the interaction between MUC1 and beta-catenin, we identified a serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to beta-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to beta-catenin and MUC1-mediated inhibition of beta-catenin degradation. Importantly, disruption of the MUC1-beta-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes transformation, at least in part, by blocking GSK3beta-mediated phosphorylation and thereby degradation of beta-catenin.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10413-22
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin.
pubmed:affiliation
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural