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Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells

Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action remains incompletely understood. Deciphering the network of Bcl-2 interacting factors is necessary to better understand the key function of Bcl-2 in apoptosis initiation. To identify novel Bcl-2 mitochondr...

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Autores principales: Villeneuve, Christelle, Baricault, Laurent, Canelle, Ludovic, Barboule, Nadia, Racca, Carine, Monsarrat, Bernard, Magnaldo, Thierry, Larminat, Florence
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069024/
https://www.ncbi.nlm.nih.gov/pubmed/21289092
http://dx.doi.org/10.1091/mbc.E10-06-0534
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author Villeneuve, Christelle
Baricault, Laurent
Canelle, Ludovic
Barboule, Nadia
Racca, Carine
Monsarrat, Bernard
Magnaldo, Thierry
Larminat, Florence
author_facet Villeneuve, Christelle
Baricault, Laurent
Canelle, Ludovic
Barboule, Nadia
Racca, Carine
Monsarrat, Bernard
Magnaldo, Thierry
Larminat, Florence
author_sort Villeneuve, Christelle
collection PubMed
description Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action remains incompletely understood. Deciphering the network of Bcl-2 interacting factors is necessary to better understand the key function of Bcl-2 in apoptosis initiation. To identify novel Bcl-2 mitochondrial partners, we have combined a Bcl-2 immunocapture with a mass spectrometry analysis using highly pure mitochondrial fractions isolated from human cancer cells. We identified at high confidence 127 potential Bcl-2–interacting proteins. Gene ontology mining reveals enrichment for mitochondrial proteins, endoplasmic reticulum–associated proteins, and cytoskeleton-associated proteins. Importantly, we report the identification of galectin-7 (Gal7), a member of a family of β-galactoside–binding lectins that was already known to exhibit a pro-apoptotic function, as a new mitochondrial Bcl-2 interacting partner. Our data further show that endogenous Bcl-2 coimmunoprecipitates with Gal7 and that recombinant Gal7 directly interacts with recombinant Bcl-2. A fraction of Gal7 is constitutively localized at mitochondria in a Bcl-2–dependent manner and sensitizes the mitochondria to the apoptotic signal. In addition, we show that the Bcl-2/Gal7 interaction is abolished following genotoxic stress. Taken together, our findings suggest that the binding of Gal7 to Bcl-2 may constitute a new target for enhancing the intrinsic apoptosis pathway.
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spelling pubmed-30690242011-06-16 Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells Villeneuve, Christelle Baricault, Laurent Canelle, Ludovic Barboule, Nadia Racca, Carine Monsarrat, Bernard Magnaldo, Thierry Larminat, Florence Mol Biol Cell Articles Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action remains incompletely understood. Deciphering the network of Bcl-2 interacting factors is necessary to better understand the key function of Bcl-2 in apoptosis initiation. To identify novel Bcl-2 mitochondrial partners, we have combined a Bcl-2 immunocapture with a mass spectrometry analysis using highly pure mitochondrial fractions isolated from human cancer cells. We identified at high confidence 127 potential Bcl-2–interacting proteins. Gene ontology mining reveals enrichment for mitochondrial proteins, endoplasmic reticulum–associated proteins, and cytoskeleton-associated proteins. Importantly, we report the identification of galectin-7 (Gal7), a member of a family of β-galactoside–binding lectins that was already known to exhibit a pro-apoptotic function, as a new mitochondrial Bcl-2 interacting partner. Our data further show that endogenous Bcl-2 coimmunoprecipitates with Gal7 and that recombinant Gal7 directly interacts with recombinant Bcl-2. A fraction of Gal7 is constitutively localized at mitochondria in a Bcl-2–dependent manner and sensitizes the mitochondria to the apoptotic signal. In addition, we show that the Bcl-2/Gal7 interaction is abolished following genotoxic stress. Taken together, our findings suggest that the binding of Gal7 to Bcl-2 may constitute a new target for enhancing the intrinsic apoptosis pathway. The American Society for Cell Biology 2011-04-01 /pmc/articles/PMC3069024/ /pubmed/21289092 http://dx.doi.org/10.1091/mbc.E10-06-0534 Text en © 2011 Villeneuve et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Villeneuve, Christelle
Baricault, Laurent
Canelle, Ludovic
Barboule, Nadia
Racca, Carine
Monsarrat, Bernard
Magnaldo, Thierry
Larminat, Florence
Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title_full Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title_fullStr Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title_full_unstemmed Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title_short Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
title_sort mitochondrial proteomic approach reveals galectin-7 as a novel bcl-2 binding protein in human cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069024/
https://www.ncbi.nlm.nih.gov/pubmed/21289092
http://dx.doi.org/10.1091/mbc.E10-06-0534
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