title: Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model.
abstract: Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.
authors.affiliation: Biomedical Biotechnology Research Unit, Department of Biochemistry, Microbiology and Biotechnology, PO Box 94, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Leanne C
authors.initials: LC
authors.lastname: Cooper
authors.forename: Earl
authors.initials: E
authors.lastname: Prinsloo
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Edkins
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
mesh_terms: D060466:Axin Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008954:Models, Biological; D010766:Phosphorylation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; C493165:HSP90AB1 protein, human; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3