NEW EMBO MEMBER'S REVIEW: Functional aspects of protein mono-ADP-ribosylation

Abstract

Mono‐ADP‐ribosylation is the enzymatic transfer of ADP‐ribose from NAD+ to acceptor proteins. It is catalysed by cellular ADP‐ribosyltransferases and certain bacterial toxins. There are two subclasses of cellular enzymes: the ectoenzymes that modify targets such as integrins, defensin and other cell surface molecules; and the intracellular enzymes that act on proteins involved in cell signalling and metabolism, such as the β‐subunit of heterotrimeric G proteins, GRP78/BiP and elongation factor 2. The genes that encode the ectoenzymes have been cloned and their protein products are well characterized, yet little is known about the intracellular ADP‐ribosyltransferases, which may be part of a novel protein family with an important role in regulating cell function. ADP‐ribosylation usually leads to protein inactivation, providing a mechanism to inhibit protein functions in both physiological and pathological conditions.

Arabidopsis RADICAL-INDUCED CELL DEATH1 Belongs to the WWE Protein–Protein Interaction Domain Protein Family and Modulates Abscisic Acid, Ethylene, and Methyl Jasmonate Responses

“…However, RCD1 does not have the conserved zinc-finger domains typical of a classical PARP; thus, it most likely has functions distinct from the classical PARP. The PARP domain protein family also contains a distinct, but less-known subfamily of mono(ADPribosyl)transferases that modify their targets by the addition of a single ADP-ribose unit (Smith, 2001;Corda and Di Girolamo, 2003). In animals, mono-ADP-ribosylation of intracellular components by intracellular mono-ADP-ribosyltransferases is just becoming an established process involved in the regulation of protein activity, although so far only genes coding for the extracellular mono-ADP-ribosyltransferases have been identified (Corda and Di Girolamo, 2003).…”

“…The PARP domain protein family also contains a distinct, but less-known subfamily of mono(ADPribosyl)transferases that modify their targets by the addition of a single ADP-ribose unit (Smith, 2001;Corda and Di Girolamo, 2003). In animals, mono-ADP-ribosylation of intracellular components by intracellular mono-ADP-ribosyltransferases is just becoming an established process involved in the regulation of protein activity, although so far only genes coding for the extracellular mono-ADP-ribosyltransferases have been identified (Corda and Di Girolamo, 2003). It could be that RCD1 is one of the predicted (Corda and Di Girolamo, 2003) intracellular plant mono-ADP-ribosyltransferases and inactivates/activates its target proteins by ADP-ribosylation.…”

“…In animals, mono-ADP-ribosylation of intracellular components by intracellular mono-ADP-ribosyltransferases is just becoming an established process involved in the regulation of protein activity, although so far only genes coding for the extracellular mono-ADP-ribosyltransferases have been identified (Corda and Di Girolamo, 2003). It could be that RCD1 is one of the predicted (Corda and Di Girolamo, 2003) intracellular plant mono-ADP-ribosyltransferases and inactivates/activates its target proteins by ADP-ribosylation. An intriguing connection is that some bacterial toxins, for example the cholera toxin, are ADPribose transferases that increase the activation of trimeric G-protein by ADP-ribosylation.…”

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

“…NAD-dependent ADP-ribosylation is a reversible PTM in which mono-and polyADP-ribosyltransferases (ARTs and PARPs) and ADP-ribosylhydrolases (ARHs) and poly(ADP-ribose) glycohydrolases (PARGs) catalyze amino acid-specific ADPribosylation and de-ADP-ribosylation, respectively ( Fig. 1) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). ADP-ribosylation has attracted attention because bacterial virulence factors, including diphtheria, cholera, and pertussis toxin, use it as part of their pathogenic mechanism (2,11).…”

“…ADP-ribosylation has attracted attention because bacterial virulence factors, including diphtheria, cholera, and pertussis toxin, use it as part of their pathogenic mechanism (2,11). Mono-and polyADP-ribosylation have been recognized also as regulatory mechanisms in many cellular processes, including DNA-repair, chromatin decondensation, transcription, telomere function, mitotic spindle formation, and apoptosis (5)(6)(7)(8)(9)(10)12).…”