Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif

Raphaël Beck, Nicolas Dejeans, Christophe Glorieux, Mélanie Creton, Edouard Delaive, Marc Dieu, Martine Raes, Philippe Levêque, Bernard Gallez, Matthieu Depuydt, Jean François Collet, Pedro Buc Calderon, Julien Verrax

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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 trapping. Using a proteomic analysis, we determined that the cleavage occurs in a conserved motif of the N-terminal nucleotide binding site, between Ile-126 and Gly-127 in Hsp90β, and between Ile-131 and Gly-132 in Hsp90α. Given the importance of Hsp90 in diverse biological functions, these findings shed new light on how oxidative stress can affect cellular homeostasis.

Original languageEnglish
Article numbere40795
JournalPLoS ONE
Volume7
Issue number7
DOIs
Publication statusPublished - 27 Jul 2012

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amino acid motifs
Amino Acid Motifs
Oxidative stress
reactive oxygen species
Reactive Oxygen Species
Oxidative Stress
oxidative stress
Amino Acids
Spin Trapping
Proteins
proteins
Proteomics
proteomics
Oxidation-Reduction
Free Radicals
binding sites
homeostasis
Homeostasis
Nucleotides
Iron

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Beck, Raphaël ; Dejeans, Nicolas ; Glorieux, Christophe ; Creton, Mélanie ; Delaive, Edouard ; Dieu, Marc ; Raes, Martine ; Levêque, Philippe ; Gallez, Bernard ; Depuydt, Matthieu ; Collet, Jean François ; Calderon, Pedro Buc ; Verrax, Julien. / Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. In: PLoS ONE. 2012 ; Vol. 7, No. 7.
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Beck, R, Dejeans, N, Glorieux, C, Creton, M, Delaive, E, Dieu, M, Raes, M, Levêque, P, Gallez, B, Depuydt, M, Collet, JF, Calderon, PB & Verrax, J 2012, 'Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif', PLoS ONE, vol. 7, no. 7, e40795. https://doi.org/10.1371/journal.pone.0040795

Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. / Beck, Raphaël; Dejeans, Nicolas; Glorieux, Christophe; Creton, Mélanie; Delaive, Edouard; Dieu, Marc; Raes, Martine; Levêque, Philippe; Gallez, Bernard; Depuydt, Matthieu; Collet, Jean François; Calderon, Pedro Buc; Verrax, Julien.

In: PLoS ONE, Vol. 7, No. 7, e40795, 27.07.2012.

Research output: Contribution to journalArticle

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AU - Beck, Raphaël

AU - Dejeans, Nicolas

AU - Glorieux, Christophe

AU - Creton, Mélanie

AU - Delaive, Edouard

AU - Dieu, Marc

AU - Raes, Martine

AU - Levêque, Philippe

AU - Gallez, Bernard

AU - Depuydt, Matthieu

AU - Collet, Jean François

AU - Calderon, Pedro Buc

AU - Verrax, Julien

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