Emerging Concepts on the Role of ADP-Ribosylation

NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways, since
it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox
reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions,
and a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl
groups from proteins. NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in the
release and signaling of Ca++, and of diadenosine tetraphosphate (Ap4A) and oligoadenylates
(oligo2'-5'A)--two immune response-activating compounds. In the biological systems considered
in this review, NAD+ is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review,
the roles of these chemical products are discussed in biological systems, such as in animals, plants,
fungi and bacteria. In the review, ADP-ribosylating enzymes are introduced, as well as the
importance to restore the NAD+ pools in these systems. Finally, a special attention is presently
focused on viral macrodomains, aimed to develop inhibitors to improve the immune response to
viruses.