Endogenous ADP-Ribosylation of Proteins at Cysteine Residues

Abstract

NAD⁺ is a substrate for many dehydrogenases that catalyze hydride transfer reactions central to energy metabolism. It is also the substrate for enzymes that catalyze the cleavage of the linkage between nicotinamide and ribose and the transfer of ADP-ribose to a nucleophilic acceptor. Such ADP-ribose transfer reactions represent a versatile mechanism for the posttranslational modification of proteins. For example, poly(ADP-ribose) polymerase catalyzes transfer of ADP-ribose to protein carboxylate groups and to the ribosyl hydroxyls of ADP-ribose resulting in the modification of proteins with ADP-ribose polymers (1). While all other ADP-ribose transfer enzymes catalyze the transfer of only single ADP-ribose groups to an acceptor, they also show a wide range of specificity for acceptors. The best understood mono-ADP-ribosyl transferases are the bacterial toxins which transfer ADP-ribose to specific amino acid residues of specific target proteins including arginine, modifed histidine and cysteine residues (2–10). However, several endogenous mono-ADP-ribosyl transferases also have been detected that have the same range of amino acid acceptor specificity as those exhibited by the bacterial toxins (11–14).