Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model

被引：27
作者：
Cooper, Leanne C. [1 ]
Prinsloo, Earl [1 ]
Edkins, Adrienne L. [1 ]
Blatch, Gregory L. [1 ,2 ]
机构：
[1] Rhodes Univ, Dept Biochem Microbiol & Biotechnol, Biomed Biotechnol Res Unit, ZA-6140 Grahamstown, South Africa
[2] Victoria Univ, Fac Hlth Engn & Sci, Sch Biomed & Hlth Sci, Melbourne, Vic 8001, Australia
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 413卷 / 04期
基金：
新加坡国家研究基金会; 美国安德鲁·梅隆基金会;
关键词：
Hsp90; GSK3; beta; Axin1; beta-Catenin; Breast cancer; BETA-CATENIN; SIGNAL-TRANSDUCTION; WNT PATHWAY; HSP90; PHOSPHORYLATION; ACTIVATION; GSK3-BETA; DEGRADATION; INHIBITION; MICROSCOPY;
D O I：
10.1016/j.bbrc.2011.08.136
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Hsp90 alpha/beta, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90 alpha/beta with its client kinases form the framework of multiple signalling networks. GSK3 beta, a known Hsp90 alpha/beta client, mediates beta-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-beta-catenin to the 26S proteasome. The canonical Wnt/beta-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90 alpha/beta involvement in Wnt/beta-catenin signalling needs clarification. Here, we describe the association of Hsp90 alpha/beta with GSK3 beta, beta-catenin, phospho-beta-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90 alpha/beta, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90 alpha/beta modulates the phosphorylation of beta-catenin by interaction in common complex with GSK3 beta/axin1/beta-catenin. (C) 201 1 Elsevier Inc. All rights reserved.
引用
收藏
页码：550 / 554
页数：5
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