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

被引：11

作者：

Abplanalp, Jeannette ^{[1
,2
]}

Leutert, Mario ^{[1
,2
]}

Frugier, Emilie ^{[3
]}

Nowak, Kathrin ^{[1
,2
]}

Feurer, Roxane ^{[1
]}

Kato, Jiro ^{[4
]}

Kistemaker, Hans V. A. ^{[5
]}

Filippov, Dmitri V. ^{[5
]}

Moss, Joel ^{[4
]}

Caflisch, Amedeo ^{[3
]}

Hottiger, Michael O. ^{[1
]}

机构：

[1] Univ Zurich, Dept Mol Mech Dis, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[2] Zurich Grad Sch, Mol Life Sci PhD Program Life Sci, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[3] Univ Zurich, Dept Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[4] NHLBI, Lab Translat Res, NIH, Bethesda, MD 20892 USA

[5] Leiden Univ, Dept Bioorgan Synth, Leiden Inst Chem, Einsteinweg 55, NL-2333 CC Leiden, Netherlands

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

瑞士国家科学基金会;

关键词：

LYSINE RESIDUES; RIBOSE; POLY(ADP-RIBOSE); RIBOSYLATION; IDENTIFICATION; GLYCOHYDROLASE; PROTEINS; FAMILY; DEGRADATION; PRODUCT;

D O I：

10.1038/s41467-017-02253-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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