|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2001-9-4
|
|
pubmed:abstractText |
Phosphorylation on a serine or threonine residue preceding proline (Ser/Thr-Pro) is a key regulatory mechanism, and the conformation of certain phosphorylated Ser/Thr-Pro bonds is regulated specifically by the prolyl isomerase Pin1. Whereas the inhibition of Pin1 induces apoptosis, Pin1 is strikingly overexpressed in a subset of human tumours. Here we show that Pin1 regulates beta-catenin turnover and subcellular localization by interfering with its interaction with adenomatous polyposis coli protein (APC). A differential-display screen reveals that Pin1 increases the transcription of several beta-catenin target genes, including those encoding cyclin D1 and c-Myc. Manipulation of Pin1 levels affects the stability of beta-catenin in vitro. Furthermore, beta-catenin levels are decreased in Pin1-deficient mice but are increased and correlated with Pin1 overexpression in human breast cancer. Pin1 directly binds a phosphorylated Ser-Pro motif next to the APC-binding site in beta-catenin, inhibits its interaction with APC and increases its translocation into the nucleus. Thus, Pin1 is a novel regulator of beta-catenin signalling and its overexpression might contribute to the upregulation of beta-catenin in tumours such as breast cancer, in which APC or beta-catenin mutations are not common.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NIMA-interacting peptidylprolyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidylprolyl Isomerase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphothreonine,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
1465-7392
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
3
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
793-801
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11533658-Adenomatous Polyposis Coli,
pubmed-meshheading:11533658-Amino Acid Sequence,
pubmed-meshheading:11533658-Amino Acid Substitution,
pubmed-meshheading:11533658-Cadherins,
pubmed-meshheading:11533658-Cell Nucleus,
pubmed-meshheading:11533658-Cytoskeletal Proteins,
pubmed-meshheading:11533658-Gene Expression Regulation,
pubmed-meshheading:11533658-Genes, Reporter,
pubmed-meshheading:11533658-HeLa Cells,
pubmed-meshheading:11533658-Humans,
pubmed-meshheading:11533658-Kinetics,
pubmed-meshheading:11533658-Mutagenesis, Site-Directed,
pubmed-meshheading:11533658-Peptidylprolyl Isomerase,
pubmed-meshheading:11533658-Phosphorylation,
pubmed-meshheading:11533658-Phosphothreonine,
pubmed-meshheading:11533658-Protein Transport,
pubmed-meshheading:11533658-Recombinant Fusion Proteins,
pubmed-meshheading:11533658-Recombinant Proteins,
pubmed-meshheading:11533658-Trans-Activators,
pubmed-meshheading:11533658-Transfection,
pubmed-meshheading:11533658-beta Catenin
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC.
|
|
pubmed:affiliation |
Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, HIM 1047, Boston, MA 02215, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
