Emerging Concepts on the Role of ADP-Ribosylation

• Main Author: Palmiro Poltronieri
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Challenges
• Subjects: adp ribosyl transferases (arts); post-translational modification (ptm); macrodomain; adp ribose glycohydrolases (arh); adp ribose (adpr); nicotinamide adenine dinucleotide (nad+); nicotinamide (nam); m-iodobenzylguanidine (mibg)
• Online Access: https://www.mdpi.com/2078-1547/11/1/3

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.