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Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas
Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor important for regulation of programmed cell death. Glutathionylation of reactive cysteines represents an oxidative modification that can be reversed by glutaredoxins (Grxs). The goal of this study was to determine whether Fas...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654302/ https://www.ncbi.nlm.nih.gov/pubmed/19171757 http://dx.doi.org/10.1083/jcb.200807019 |
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author | Anathy, Vikas Aesif, Scott W. Guala, Amy S. Havermans, Marije Reynaert, Niki L. Ho, Ye-Shih Budd, Ralph C. Janssen-Heininger, Yvonne M.W. |
author_facet | Anathy, Vikas Aesif, Scott W. Guala, Amy S. Havermans, Marije Reynaert, Niki L. Ho, Ye-Shih Budd, Ralph C. Janssen-Heininger, Yvonne M.W. |
author_sort | Anathy, Vikas |
collection | PubMed |
description | Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor important for regulation of programmed cell death. Glutathionylation of reactive cysteines represents an oxidative modification that can be reversed by glutaredoxins (Grxs). The goal of this study was to determine whether Fas is redox regulated under physiological conditions. In this study, we demonstrate that stimulation with Fas ligand (FasL) induces S-glutathionylation of Fas at cysteine 294 independently of nicotinamide adenine dinucleotide phosphate reduced oxidase–induced ROS. Instead, Fas is S-glutathionylated after caspase-dependent degradation of Grx1, increasing subsequent caspase activation and apoptosis. Conversely, overexpression of Grx1 attenuates S-glutathionylation of Fas and partially protects against FasL-induced apoptosis. Redox-mediated Fas modification promotes its aggregation and recruitment into lipid rafts and enhances binding of FasL. As a result, death-inducing signaling complex formation is also increased, and subsequent activation of caspase-8 and -3 is augmented. These results define a novel redox-based mechanism to propagate Fas-dependent apoptosis. |
format | Text |
id | pubmed-2654302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26543022009-07-26 Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas Anathy, Vikas Aesif, Scott W. Guala, Amy S. Havermans, Marije Reynaert, Niki L. Ho, Ye-Shih Budd, Ralph C. Janssen-Heininger, Yvonne M.W. J Cell Biol Research Articles Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor important for regulation of programmed cell death. Glutathionylation of reactive cysteines represents an oxidative modification that can be reversed by glutaredoxins (Grxs). The goal of this study was to determine whether Fas is redox regulated under physiological conditions. In this study, we demonstrate that stimulation with Fas ligand (FasL) induces S-glutathionylation of Fas at cysteine 294 independently of nicotinamide adenine dinucleotide phosphate reduced oxidase–induced ROS. Instead, Fas is S-glutathionylated after caspase-dependent degradation of Grx1, increasing subsequent caspase activation and apoptosis. Conversely, overexpression of Grx1 attenuates S-glutathionylation of Fas and partially protects against FasL-induced apoptosis. Redox-mediated Fas modification promotes its aggregation and recruitment into lipid rafts and enhances binding of FasL. As a result, death-inducing signaling complex formation is also increased, and subsequent activation of caspase-8 and -3 is augmented. These results define a novel redox-based mechanism to propagate Fas-dependent apoptosis. The Rockefeller University Press 2009-01-26 /pmc/articles/PMC2654302/ /pubmed/19171757 http://dx.doi.org/10.1083/jcb.200807019 Text en © 2009 Anathy et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Anathy, Vikas Aesif, Scott W. Guala, Amy S. Havermans, Marije Reynaert, Niki L. Ho, Ye-Shih Budd, Ralph C. Janssen-Heininger, Yvonne M.W. Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title | Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title_full | Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title_fullStr | Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title_full_unstemmed | Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title_short | Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas |
title_sort | redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and s-glutathionylation of fas |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654302/ https://www.ncbi.nlm.nih.gov/pubmed/19171757 http://dx.doi.org/10.1083/jcb.200807019 |
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