Publication Date:
1999-03-26
Description:
Dysregulation of Wnt-beta-catenin signaling disrupts axis formation in vertebrate embryos and underlies multiple human malignancies. The adenomatous polyposis coli (APC) protein, axin, and glycogen synthase kinase 3beta form a Wnt-regulated signaling complex that mediates the phosphorylation-dependent degradation of beta-catenin. A protein phosphatase 2A (PP2A) regulatory subunit, B56, interacted with APC in the yeast two-hybrid system. Expression of B56 reduced the abundance of beta-catenin and inhibited transcription of beta-catenin target genes in mammalian cells and Xenopus embryo explants. The B56-dependent decrease in beta-catenin was blocked by oncogenic mutations in beta-catenin or APC, and by proteasome inhibitors. B56 may direct PP2A to dephosphorylate specific components of the APC-dependent signaling complex and thereby inhibit Wnt signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seeling, J M -- Miller, J R -- Gil, R -- Moon, R T -- White, R -- Virshup, D M -- 3P30CA42014/CA/NCI NIH HHS/ -- R01 CA71074/CA/NCI NIH HHS/ -- T32CA09602/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Mar 26;283(5410):2089-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10092233" target="_blank"〉PubMed〈/a〉
Keywords:
Adenomatous Polyposis Coli Protein
;
Animals
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Cell Line
;
Cysteine Endopeptidases/metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Cytoskeletal Proteins/genetics/*metabolism
;
Down-Regulation
;
Genes, Reporter
;
Glycogen Synthase Kinase 3
;
Glycogen Synthase Kinases
;
Humans
;
Leupeptins/pharmacology
;
Multienzyme Complexes/metabolism
;
Mutation
;
Phosphoprotein Phosphatases/chemistry/genetics/*metabolism
;
Phosphorylation
;
Proteasome Endopeptidase Complex
;
Protein Phosphatase 2
;
Proto-Oncogene Proteins/*metabolism
;
*Signal Transduction
;
*Trans-Activators
;
Transcriptional Activation
;
Transfection
;
Tumor Cells, Cultured
;
Wnt Proteins
;
Xenopus
;
Xenopus Proteins
;
*Zebrafish Proteins
;
beta Catenin
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
