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

TitleProteomic analyses identify ARH3 as a serine mono-ADP-ribosylhydrolase.
Publication TypeJournal Article
Year of Publication2017
AuthorsAbplanalp J., Leutert M., Frugier E., Nowak K., Feurer R., Kato J., Kistemaker H.VA, Filippov D.V, Moss J., Caflisch A., Hottiger M.O
JournalNature Communications
Volume8
Issue1
Pagination2055
Date Published2017 Dec 12
Type of ArticleResearch Article
ISSN2041-1723
Keywordshistone code, Histone post-translational modifications, Hydrolases, Poly(ADP-ribose) Polymerases, PolyADP-ribosylation, Proteomics
Abstract

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.

DOI10.1038/s41467-017-02253-1
pubindex

0229

Alternate JournalNat. Commun.
PubMed ID29234005
PubMed Central IDPMC5727137
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