title: Structure and function of the ARH family of ADP-ribosyl-acceptor hydrolases.
abstract: ADP-ribosylation is a post-translational protein modification, in which ADP-ribose is transferred from nicotinamide adenine dinucleotide (NAD(+)) to specific acceptors, thereby altering their activities. The ADP-ribose transfer reactions are divided into mono- and poly-(ADP-ribosyl)ation. Cellular ADP-ribosylation levels are tightly regulated by enzymes that transfer ADP-ribose to acceptor proteins (e.g., ADP-ribosyltransferases, poly-(ADP-ribose) polymerases (PARP)) and those that cleave the linkage between ADP-ribose and acceptor (e.g., ADP-ribosyl-acceptor hydrolases (ARH), poly-(ADP-ribose) glycohydrolases (PARG)), thereby constituting an ADP-ribosylation cycle. This review summarizes current findings related to the ARH family of proteins. This family comprises three members (ARH1-3) with similar size (39kDa) and amino acid sequence. ARH1 catalyzes the hydrolysis of the N-glycosidic bond of mono-(ADP-ribosyl)ated arginine. ARH3 hydrolyzes poly-(ADP-ribose) (PAR) and O-acetyl-ADP-ribose. The different substrate specificities of ARH1 and ARH3 contribute to their unique roles in the cell. Based on a phenotype analysis of ARH1(-/-) and ARH3(-/-) mice, ARH1 is involved in the action by bacterial toxins as well as in tumorigenesis. ARH3 participates in the degradation of PAR that is synthesized by PARP1 in response to oxidative stress-induced DNA damage; this hydrolytic reaction suppresses PAR-mediated cell death, a pathway termed parthanatos.
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, United States.
authors.forename: Masato
authors.initials: M
authors.lastname: Mashimo
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, United States.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kato
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, United States. Electronic address: mossj@nhlbi.nih.gov.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C469745:LDLRAP1 protein, human; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D006026:Glycoside Hydrolases; C508145:ADPRS protein, human; C022407:poly ADP-ribose glycohydrolase; D009699:N-Glycosyl Hydrolases; C000599892:ARH1 protein, mouse
keywords: ADP-ribose-acceptor hydrolase; ADP-ribosylation; ARH; Cholera toxin; Parthanatos; Tumorigenesis
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