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Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase

ADP-ribosylation is a posttranslational modification that exists in monomeric and polymeric forms. Whereas the writers (e.g. ARTD1/PARP1) and erasers (e.g. PARG, ARH3) of poly-ADP-ribosylation (PARylation) are relatively well described, the enzymes involved in mono-ADP-ribosylation (MARylation) have...

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Autores principales: Abplanalp, Jeannette, Leutert, Mario, Frugier, Emilie, Nowak, Kathrin, Feurer, Roxane, Kato, Jiro, Kistemaker, Hans V. A., Filippov, Dmitri V., Moss, Joel, Caflisch, Amedeo, Hottiger, Michael O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727137/
https://www.ncbi.nlm.nih.gov/pubmed/29234005
http://dx.doi.org/10.1038/s41467-017-02253-1
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author Abplanalp, Jeannette
Leutert, Mario
Frugier, Emilie
Nowak, Kathrin
Feurer, Roxane
Kato, Jiro
Kistemaker, Hans V. A.
Filippov, Dmitri V.
Moss, Joel
Caflisch, Amedeo
Hottiger, Michael O.
author_facet Abplanalp, Jeannette
Leutert, Mario
Frugier, Emilie
Nowak, Kathrin
Feurer, Roxane
Kato, Jiro
Kistemaker, Hans V. A.
Filippov, Dmitri V.
Moss, Joel
Caflisch, Amedeo
Hottiger, Michael O.
author_sort Abplanalp, Jeannette
collection PubMed
description ADP-ribosylation is a posttranslational modification that exists in monomeric and polymeric forms. Whereas the writers (e.g. ARTD1/PARP1) and erasers (e.g. PARG, ARH3) of poly-ADP-ribosylation (PARylation) are relatively well described, the enzymes involved in mono-ADP-ribosylation (MARylation) have been less well investigated. While erasers for the MARylation of glutamate/aspartate and arginine have been identified, the respective enzymes with specificity for serine were missing. Here we report that, in vitro, ARH3 specifically binds and demodifies proteins and peptides that are MARylated. Molecular modeling and site-directed mutagenesis of ARH3 revealed that numerous residues are critical for both the mono- and the poly-ADP-ribosylhydrolase activity of ARH3. Notably, a mass spectrometric approach showed that ARH3-deficient mouse embryonic fibroblasts are characterized by a specific increase in serine-ADP-ribosylation in vivo under untreated conditions as well as following hydrogen peroxide stress. Together, our results establish ARH3 as a serine mono-ADP-ribosylhydrolase and as an important regulator of the basal and stress-induced ADP-ribosylome.
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spelling pubmed-57271372017-12-14 Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase Abplanalp, Jeannette Leutert, Mario Frugier, Emilie Nowak, Kathrin Feurer, Roxane Kato, Jiro Kistemaker, Hans V. A. Filippov, Dmitri V. Moss, Joel Caflisch, Amedeo Hottiger, Michael O. Nat Commun Article ADP-ribosylation is a posttranslational modification that exists in monomeric and polymeric forms. Whereas the writers (e.g. ARTD1/PARP1) and erasers (e.g. PARG, ARH3) of poly-ADP-ribosylation (PARylation) are relatively well described, the enzymes involved in mono-ADP-ribosylation (MARylation) have been less well investigated. While erasers for the MARylation of glutamate/aspartate and arginine have been identified, the respective enzymes with specificity for serine were missing. Here we report that, in vitro, ARH3 specifically binds and demodifies proteins and peptides that are MARylated. Molecular modeling and site-directed mutagenesis of ARH3 revealed that numerous residues are critical for both the mono- and the poly-ADP-ribosylhydrolase activity of ARH3. Notably, a mass spectrometric approach showed that ARH3-deficient mouse embryonic fibroblasts are characterized by a specific increase in serine-ADP-ribosylation in vivo under untreated conditions as well as following hydrogen peroxide stress. Together, our results establish ARH3 as a serine mono-ADP-ribosylhydrolase and as an important regulator of the basal and stress-induced ADP-ribosylome. Nature Publishing Group UK 2017-12-12 /pmc/articles/PMC5727137/ /pubmed/29234005 http://dx.doi.org/10.1038/s41467-017-02253-1 Text en © The Author(s) 2017 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
Abplanalp, Jeannette
Leutert, Mario
Frugier, Emilie
Nowak, Kathrin
Feurer, Roxane
Kato, Jiro
Kistemaker, Hans V. A.
Filippov, Dmitri V.
Moss, Joel
Caflisch, Amedeo
Hottiger, Michael O.
Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title_full Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title_fullStr Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title_full_unstemmed Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title_short Proteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase
title_sort proteomic analyses identify arh3 as a serine mono-adp-ribosylhydrolase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727137/
https://www.ncbi.nlm.nih.gov/pubmed/29234005
http://dx.doi.org/10.1038/s41467-017-02253-1
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