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 beta-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.

Fig. 1. A schematic representation of the reversible mono-ADP-ribosylation reaction catalysed by an arginine-specific mono-ADP-ribosyltransferase and an ADP-ribosylhydrolase (see text for details). Other amino acid residues that can be modified by this reaction are cysteine, diphtamide and asparagine (Okazaki and Moss, 1999; Table I).