Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif.
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 r...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3407180?pdf=render |
| _version_ | 1819037675988975616 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Raphaël Beck |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:25:12Z |
| format | Article |
| id | doaj.art-55c66410e612439b9c46d5ac3219c40a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:25:12Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-55c66410e612439b9c46d5ac3219c40a2022-12-21T19:10:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4079510.1371/journal.pone.0040795Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif.Raphaël BeckNicolas DejeansChristophe GlorieuxMélanie CretonEdouard DelaiveMarc DieuMartine RaesPhilippe LevêqueBernard GallezMatthieu DepuydtJean-François ColletPedro Buc CalderonJulien VerraxHsp90 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.http://europepmc.org/articles/PMC3407180?pdf=render |
| spellingShingle | 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 Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. PLoS ONE |
| title | Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. |
| title_full | Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. |
| title_fullStr | Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. |
| title_full_unstemmed | Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. |
| title_short | Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif. |
| title_sort | hsp90 is cleaved by reactive oxygen species at a highly conserved n terminal amino acid motif |
| url | http://europepmc.org/articles/PMC3407180?pdf=render |
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