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: Leanne C Cooper, Earl Prinsloo, Adrienne L Edkins, Gregory L Blatch
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 413 Issue 4 Pg. 550-4 (Oct 07 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21925151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• AXIN1 protein, human
• Axin Protein
• HSP90 Heat-Shock Proteins
• HSP90AA2P protein, human
• HSP90AB1 protein, human
• beta Catenin
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Axin Protein (metabolism)
• Breast Neoplasms (metabolism)
• Carcinoma (metabolism)
• Cell Line, Tumor
• Epithelial Cells (metabolism)
• Female
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• HSP90 Heat-Shock Proteins (metabolism)
• Humans
• Immunoprecipitation
• Models, Biological
• Phosphorylation
• beta Catenin (metabolism)