The ADP-Ribosyl-Transferases Diphtheria Toxin-Like (ARTDs) Family: An Overview

Abstract

Poly-ADP-ribosylation is a post-translational modification that occurs in multicellular organisms, including plants and some lower unicellular eukaryotes. The founding member of the PARP family is PARP1. To date, 17 members of the PARP family have been identified, which differ from each other in terms of domain organization, transmodification targets, cellular localization, and biological functions. In recent years, considering structural and biochemical features of the different members of the PARP family, a new classification has been proposed. Thus, enzymes firstly classified as PARP are now named diphtheria-toxin-like ARTs, abbreviated to ARTDs, in accordance with the prototype bacterial toxin that their structural aspects resemble, with numbers indicating the different proteins of the family. The 17 human ARTD enzymes can be divided on the basis of their catalytic activity into polymerases (ARTD1-6), mono-ADP-ribosyl-transferases (ARTD7-17), and the inactive ARTD13. In recent years, ADP-ribosylation was intensively studied, and research was dominated by studies focusing on the role of this modification and its implication on various cellular processes. The aim of this review is to provide a general overview of the ARTD enzymes, with a special focus on mono-ARTDs.

PARPs in genome stability and signal transduction: implications for cancer therapy

“…PARPs are located in various cellular compartments and regulate major cellular functions, e.g. DNA damage response, transcription, chromatin structure regulation, UPR, metabolism, mitosis, telomere length maintenance, stress granule formation, antiviral response, and receptor-associated signalling [5–9,11,12,15,16,18].…”

“…Substrates of ADPr can be either proteins or nucleic acids [2–4]. ARTs are widespread in different organisms and regulate diverse cellular processes as the DNA damage response (DDR), transcription, RNA metabolism and antiviral response, cell division, unfolded protein response (UPR), stress granule formation, metabolism, and cell death to cite a few [5–18].…”

PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis

“… 15–17 PARPs that catalyse MARylation have been shown to have amino acid substitutions at their catalytic centres that enable them to attach only MAR moieties to the target proteins. 18 , 19 MARylation has been shown to play a role in intracellular signalling, including inflammatory and stress responses. 19–21 …”

Role of mono‑ADP‑ribosylation histone modification (Review)

“…Certain ARTs modify proteins with chains of poly ADP-ribose or with mono ADP-ribose (mADPr) ( Table I ). According to the different structures of the catalytic domains, ARTs are divided into bacterial diphtheria toxin-like ARTs (ARTDs) ( 16 ) and clostridial C2 and C3 toxin-like ARTs (ARTCs) ( 17 ). ARTDs, which were previously termed the poly(ADP-ribose) polymerase (PARP) family and include 17 members ( 18 , 19 ), are widely distributed in cells and are mostly concentrated in the nucleus.…”

“…ARTDs, which were previously termed the poly(ADP-ribose) polymerase (PARP) family and include 17 members ( 18 , 19 ), are widely distributed in cells and are mostly concentrated in the nucleus. Compared with ARTD1-6 possessing, ARTD7-17 (except ARTD13, which is catalytically inactive) only catalyzes mono-ADP-ribosylation ( 16 , 20 ), due to the absence of conserved glutamate. In addition, ARTD3 has been detected as a mono-ADP-ribosyltransferase in previous studies ( 21 ).…”