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Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition
Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. O...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840378/ https://www.ncbi.nlm.nih.gov/pubmed/29511177 http://dx.doi.org/10.1038/s41419-018-0408-1 |
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author | Elena-Real, Carlos A. Díaz-Quintana, Antonio González-Arzola, Katiuska Velázquez-Campoy, Adrián Orzáez, Mar López-Rivas, Abelardo Gil-Caballero, Sergio De la Rosa, Miguel Á. Díaz-Moreno, Irene |
author_facet | Elena-Real, Carlos A. Díaz-Quintana, Antonio González-Arzola, Katiuska Velázquez-Campoy, Adrián Orzáez, Mar López-Rivas, Abelardo Gil-Caballero, Sergio De la Rosa, Miguel Á. Díaz-Moreno, Irene |
author_sort | Elena-Real, Carlos A. |
collection | PubMed |
description | Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3ε (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3ε interaction and show the ability of cytochrome c to block 14-3-3ε-mediated Apaf-1 inhibition, thereby unveiling a novel function for cytochrome c as an indirect activator of caspase-9/3. We have used calorimetry, NMR spectroscopy, site mutagenesis and computational calculations to provide an insight into the structural features of the cytochrome c / 14-3-3ε complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network. |
format | Online Article Text |
id | pubmed-5840378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58403782018-03-08 Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition Elena-Real, Carlos A. Díaz-Quintana, Antonio González-Arzola, Katiuska Velázquez-Campoy, Adrián Orzáez, Mar López-Rivas, Abelardo Gil-Caballero, Sergio De la Rosa, Miguel Á. Díaz-Moreno, Irene Cell Death Dis Article Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3ε (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3ε interaction and show the ability of cytochrome c to block 14-3-3ε-mediated Apaf-1 inhibition, thereby unveiling a novel function for cytochrome c as an indirect activator of caspase-9/3. We have used calorimetry, NMR spectroscopy, site mutagenesis and computational calculations to provide an insight into the structural features of the cytochrome c / 14-3-3ε complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network. Nature Publishing Group UK 2018-03-06 /pmc/articles/PMC5840378/ /pubmed/29511177 http://dx.doi.org/10.1038/s41419-018-0408-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Elena-Real, Carlos A. Díaz-Quintana, Antonio González-Arzola, Katiuska Velázquez-Campoy, Adrián Orzáez, Mar López-Rivas, Abelardo Gil-Caballero, Sergio De la Rosa, Miguel Á. Díaz-Moreno, Irene Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title | Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title_full | Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title_fullStr | Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title_full_unstemmed | Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title_short | Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition |
title_sort | cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent apaf-1 inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840378/ https://www.ncbi.nlm.nih.gov/pubmed/29511177 http://dx.doi.org/10.1038/s41419-018-0408-1 |
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