ADP-ribose. A historical overview.

ADP-ribosylation of proteins was first detected as a modification of nuclear proteins by polymeric ADP-ribose residues derived from NAD+. Subsequently, the field developed into three destinct sections: (i) Possible function(s) of poly-ADP-ribosylation with increasing evidence for participation in DNA excision repair and perhaps in DNA recombination; (ii) Mono-ADP-ribosylation as a mechanism to inactivate (by some toxins) or to regulate enzymes/proteins (e.g. in bacterial nitrogen fixation, in protein traffic through membranes, in intercellular communication); (iii) Intramolecular ADP-ribosylation converting NAD+ to cyclic ADP-ribose, a possible Ca(2+)-mobilizing agonist. Thus, NAD+ first known as a cofactor of oxidoreductases has experienced an impressive metamorphosis from a housekeeping coenzyme to a multifunctional group transfering metabolite involved in an increasing number of intracellular and intercellular regulatory loops.