ribosylation

Ribosylation is a biochemical modification in which ribose-containing groups are attached to target molecules, most often as ADP-ribose units transferred from nicotinamide adenine dinucleotide (NAD+) to acceptors such as proteins or nucleic acids. The modification can be mono-ADP-ribosylation (MARylation) or poly-ADP-ribosylation (PARylation), the latter forming chains of ADP-ribose.

Enzymes responsible for ribosylation are ADP-ribosyltransferases (ARTs). In eukaryotes, the PARP family mainly mediates PARylation, while other ARTs catalyze MARylation. Bacterial toxins also employ ARTs to modify host proteins and disrupt signaling. Acceptor residues include arginine, serine, cysteine, and various other side chains, with enzyme context determining the specific target.

Ribosylation participates in diverse cellular processes. PARP enzymes are central to DNA damage sensing and repair, chromatin remodeling, transcriptional regulation, and cellular stress responses. MARylation can influence protein interactions and signaling pathways. In host-pathogen interactions, toxin-catalyzed ribosylation is a mechanism of virulence that alters host cell function.

Reversibility and detection are important aspects of ribosylation. ADP-ribose units can be removed by specific hydrolases; PARG degrades PAR chains, while other enzymes can reverse MAR attachments. Detection methods include antibodies against PAR or MAR and mass spectrometry-based approaches.

Clinically, inhibition of PARP enzymes has therapeutic value, particularly in BRCA1/2-deficient cancers, where it impairs DNA repair and can promote tumor cell death. PARP inhibitors are approved in several settings, and ongoing research explores additional indications and combination strategies.