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ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties.[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

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.[5] These reactions are reversible; for example, when arginine is modified, the ADP-ribosylarginine produced can be removed by ADP-ribosylarginine hydrolases.[6]

ADP-ribose can also be transferred to proteins in 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

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.[9]

See also


  1. Belenky P, Bogan KL, Brenner C (2007). "NAD+ metabolism in health and disease" (PDF). Trends Biochem. Sci. 32 (1): 12–9. 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. 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. PMID 15003268.
  4. Corda D, Di Girolamo M (2003). "Functional aspects of protein mono-ADP-ribosylation". EMBO J. 22 (9): 1953–8. 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. PMID 10448534.
  6. Takada T, Okazaki IJ, Moss J (1994). "ADP-ribosylarginine hydrolases". Mol. Cell. Biochem. 138 (1–2): 119–22. PMID 7898453.
  7. 7.0 7.1 Diefenbach J, Bürkle A (2005). "Introduction to poly(ADP-ribose) metabolism". Cell. Mol. Life Sci. 62 (7–8): 721–30. PMID 15868397.
  8. 8.0 8.1 Burkle A (2005). "Poly(ADP-ribose). The most elaborate metabolite of NAD+". FEBS J. 272 (18): 4576–89. 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. PMID 15204437.