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ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein.[1][2] These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.[3][4]

ADP-ribosylation enzymes[edit]

One way this protein modification can be produced is by NAD+:diphthamide ADP-ribosyltransferase enzymes, which transfer the ADP-ribose group from nicotinamide adenine dinucleotide (NAD+) onto acceptors such as arginine, glutamic acid, or aspartic acid. In humans, one type of ADP-ribosyltransferases is the NAD:arginine ADP-ribosyltransferases, which modify amino acid residues in proteins such as histones by adding a single ADP-ribose group.[5] These reactions are reversible; for example, when arginine is modified, the ADP-ribosylarginine produced can be removed by ADP-ribosylarginine hydrolases.[6]

Multiple groups of ADP-ribose moieties can also be transferred to proteins to form long branched chains, in a reaction called poly(ADP-ribosyl)ation.[7] This protein modification is carried out by the poly ADP-ribose polymerases (PARPs), which are found in most eukaryotes, but not prokaryotes or yeast.[7][8] 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.[8]

Bacterial toxins[edit]

ADP-ribosylation is also responsible for the actions of some bacterial toxins, such as cholera toxin, diphtheria toxin, pertussis toxin, Clostridium botulinum C3 toxin and heat-labile enterotoxin. These toxin proteins are ADP-ribosyltransferases that modify target proteins in human cells. For example, cholera toxin ADP-ribosylates G proteins, causing massive fluid secretion from the lining of the small intestine, resulting in life-threatening diarrhea. P. aeruginosa ADP-ribosylates cytoskeleton and GTP-binding proteins.[9]

Antibiotic resistance[edit]

Bacteria, including both pathogens and environmental strains, have an enzyme, Arr, which inactivates rifampin by ADP-ribosylation and thus conferring antibiotic resistance.

See also[edit]


  1. ^ Belenky P, Bogan KL, Brenner C (2007). "NAD+ metabolism in health and disease". Trends Biochem. Sci. 32 (1): 12–9. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. 
  2. ^ Ziegler M (2000). "New functions of a long-known molecule. Emerging roles of NAD in cellular signaling". Eur. J. Biochem. 267 (6): 1550–64. doi:10.1046/j.1432-1327.2000.01187.x. PMID 10712584. 
  3. ^ Berger F, Ramírez-Hernández MH, Ziegler M (2004). "The new life of a centenarian: signalling functions of NAD(P)". Trends Biochem. Sci. 29 (3): 111–8. doi:10.1016/j.tibs.2004.01.007. PMID 15003268. 
  4. ^ Corda D, Di Girolamo M (2003). "NEW EMBO MEMBER'S REVIEW: Functional aspects of protein mono-ADP-ribosylation". EMBO J. 22 (9): 1953–8. doi:10.1093/emboj/cdg209. PMC 156081. PMID 12727863. 
  5. ^ Okazaki IJ, Moss J (1999). "Characterization of glycosylphosphatidylinositiol-anchored, secreted, and intracellular vertebrate mono-ADP-ribosyltransferases". Annual Review of Nutrition 19: 485–509. doi:10.1146/annurev.nutr.19.1.485. PMID 10448534. 
  6. ^ Takada T, Okazaki IJ, Moss J (1994). "ADP-ribosylarginine hydrolases". Mol. Cell. Biochem. 138 (1–2): 119–22. doi:10.1007/BF00928452. PMID 7898453. 
  7. ^ a b Diefenbach J, Bürkle A (2005). "Introduction to poly(ADP-ribose) metabolism". Cell. Mol. Life Sci. 62 (7–8): 721–30. doi:10.1007/s00018-004-4503-3. PMID 15868397. 
  8. ^ a b Burkle A (2005). "Poly(ADP-ribose). The most elaborate metabolite of NAD+". FEBS J. 272 (18): 4576–89. doi:10.1111/j.1742-4658.2005.04864.x. PMID 16156780. 
  9. ^ De Haan L, Hirst TR (2004). "Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review)". Mol. Membr. Biol. 21 (2): 77–92. doi:10.1080/09687680410001663267. PMID 15204437.