hsp90 is cleaved by reactive oxygen species at a highly conserved n-terminal amino acid motif一半是由活性氧在一个高度保守的n端氨基酸基序.pdfVIP

Hsp90 Is Cleaved by Reactive Oxygen Species at a Highly Conserved N-Terminal Amino Acid Motif ¨ 1 1 1 ´ 1 2 2 Raphael Beck , Nicolas Dejeans , Christophe Glorieux , Melanie Creton , Edouard Delaive , Marc Dieu , 2 ˆ 1 1 3 3 Martine Raes , Philippe Leveque , Bernard Gallez , Matthieu Depuydt , Jean-Franc¸ois Collet , Pedro 1,4 1 Buc Calderon , Julien Verrax * ´ ´ 1 Louvain Drug Research Institute, Universite catholique de Louvain (UCL), Brussels, Belgium, 2 Unite de Recherche en Biologie Cellulaire (URBC)-NARILIS, FUNDP- ´ University of Namur, Namur, Belgium, 3 de Duve Institute, Universite catholique de Louvain (UCL), Brussels, Belgium, 4 Departamento de Ciencias Quimicas y Farmaceuticas, Arturo Prat University, Iquique, Chile Abstract Hsp90 is an essential chaperone that is necessary for the folding, stability and activity of numerous proteins. In this study, we demonstrate that free radicals formed during oxidative stress conditions can cleave Hsp90. This cleavage occurs through a Fenton reaction which requires the presence of redox-active iron. As a result of the cleavage, we observed a disruption of the chaperoning function of Hsp90 and the degradation of its client proteins, for example, Bcr-Abl, RIP, c-Raf, NEMO and hTert. Formation of Hsp90 protein radicals on exposure to oxidative stress was confirmed by immuno-spin