ENZYMATIC AND NONENZYMATIC ADP-RIBOSYLATION OF CYSTEINE

Mono-ADP-ribosylation is a protein modification that occurs at a numbe r of different amino acids, dictated by the specificity of the individ ual ADP-ribosyltransferases. A specific cysteine in several guanine nu cleotide-binding regulatory proteins is ADP-ribosylated by the bacteri al protein pertussis toxin. Recent purification of an ADP-ribosylcyste ine hydrolase and NAD:cysteine ADP-ribosyltransferase, and detection o f ADP-ribose-cysteine linkages in tissue samples has raised hope that an endogenous regulatory cysteine-specific ADP-ribosylation pathway ex ists. A current goal is the identification of such a pathway for ADP-r ibosylation of cysteine within animal cells. Interpretation of the dat a in this field has been complicated by recent reports that revealed s everal unforeseen chemical reactions of NAD and its metabolites with f ree cysteine and cysteine in proteins. This mini-review covers the lat est understanding of the ADP-ribosylation reactions associated with cy steine, and provides a set of criteria for future research to establis h positively the existence of an endogenous cysteine-specific mono-ADP -ribosyltransferase.