ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.
This protein modification is produced by ADP-ribosyltransferase enzymes, which transfer the ADP-ribose group from nicotinamide adenine dinucleotide (NAD+) onto acceptors such as arginine, glutamic acid or aspartic acid residues in their substrate protein. In humans, one type of ADP-ribosyltransferases are the NAD:arginine ADP-ribosyltransferases, which modify amino acid residues in proteins such as histones by adding a single ADP-ribose group. These reactions are reversible; for example, when arginine is modified, the ADP-ribosylarginine produced can be removed by ADP-ribosylarginine hydrolases.
ADP-ribose can also be transferred to proteins in long branched chains, in a reaction called poly(ADP-ribosyl)ation. This protein modification is carried out by the poly ADP-ribose polymerases (PARPs) which are found in most eukaryotes, but not prokaryotes or yeast. The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance.
ADP-ribosylation is also responsible for the actions of some bacterial toxins, such as cholera toxin and pertussis toxin. These toxin proteins are ADP-ribosyltransferases that modify target proteins in human cells. For example, cholera toxin ADP-ribosylates G proteins, which causes massive fluid secretion from the lining of the small intestine and results in life-threatening diarrhea.
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