A key process in the regulation of protein activities and thus cellular signaling\npathways is the modification of proteins by post-translational mechanisms. Knowledge\nabout the enzymes (writers and erasers) that attach and remove post-translational\nmodifications, the targets that are modified and the functional consequences elicited by\nspecific modifications, is crucial for understanding cell biological processes. Moreover\ndetailed knowledge about these mechanisms and pathways helps to elucidate the molecular\ncauses of various diseases and in defining potential targets for therapeutic approaches.\nIntracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine\ndinucleotide (NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed\nby enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as\nPARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is\nrelatively well understood with inhibitors being used as anti-cancer agents. However, the\nmajority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing\nmono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADPribosylation\nhave been identified only recently, it is becoming more and more evident that this\nreversible post-translational modification is capable of modulating key intracellular processes\nand signaling pathways. These include signal transduction mechanisms, stress pathways\nassociated with the endoplasmic reticulum and stress granules, and chromatin-associated\nprocesses such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation\ncontrols, through these different pathways, the development of cancer and infectious diseases.
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