ADP-ribosylation reactions in the kingdoms of life

ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses. ADP-ribosyltransferases (ARTs) and certain sirtuins attach ADP-ribose units to target proteins, using nicotinamide adenine dinucleotide (NAD+) as a substrate. The recognition of PAR, MAR and iso-ADPr by binding proteins triggers the formation of protein complexes (interactomes), participating to various biological processes. The degradation of PAR and MAR is performed by eraser enzymes, poly ADP ribose glycohydrolases, Macro-domain proteins, and ADP-ribosyl acceptor hydrolases. Sirtuins and ARTs compete for the intracellular NAD + pool. Excessive activation of NAD + consuming enzymes in localised compartments may lead to cell death pathway or to necrosis. Bacteria (either human pathogens as well as plant pathogens) codify for ADP-ribosylating toxins, acting as effectors. Parylation dependent ubiquitination linked to protein degradation (PARdU) has been studied for Dtx3L/Parp9 complex, and for PARP5a/b (tankyrases) in association to E3 ligase RING finger protein 146 (RNF146). In some bacteria, such as Legionella pneumophila, a PARdU activity is exerted by multidomain ADP-ribosyltransferases that ubiquitinate and inactivate several cell proteins. Further deepening on presence of these enzymes in all the domains of life and novel findings on these important post-translational modifications will be discussed.