ADP-ribosylation

ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. [cite journal |author=Belenky P, Bogan KL, Brenner C |title=NAD+ metabolism in health and disease |journal=Trends Biochem. Sci. |volume=32 |issue=1 |pages=12–9 |year=2007 |pmid=17161604 |url=http://www.dartmouth.edu/~brenner/belenky07a.pdf |doi=10.1016/j.tibs.2006.11.006] [cite journal |author=Ziegler M |title=New functions of a long-known molecule. Emerging roles of NAD in cellular signaling |journal=Eur. J. Biochem. |volume=267 |issue=6 |pages=1550–64 |year=2000 |pmid=10712584 |doi=10.1046/j.1432-1327.2000.01187.x] These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis. [cite journal |author=Berger F, Ramírez-Hernández MH, Ziegler M |title=The new life of a centenarian: signalling functions of NAD(P) |journal=Trends Biochem. Sci. |volume=29 |issue=3 |pages=111–8 |year=2004 |pmid=15003268 |doi=10.1016/j.tibs.2004.01.007] [cite journal |author=Corda D, Di Girolamo M |title=Functional aspects of protein mono-ADP-ribosylation |journal=EMBO J. |volume=22 |issue=9 |pages=1953–8 |year=2003 |pmid=12727863 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12727863 |doi=10.1093/emboj/cdg209]

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. [cite journal |author=Okazaki IJ, Moss J |title=Characterization of glycosylphosphatidylinositiol-anchored, secreted, and intracellular vertebrate mono-ADP-ribosyltransferases |journal=Annual Review of Nutrition |volume=19 |pages=485–509 |year=1999 |pmid=10448534 |doi=10.1146/annurev.nutr.19.1.485 ] These reactions are reversible; for example, when arginine is modified, the ADP-ribosylarginine produced can be removed by ADP-ribosylarginine hydrolases. [cite journal |author=Takada T, Okazaki IJ, Moss J |title=ADP-ribosylarginine hydrolases |journal=Mol. Cell. Biochem. |volume=138 |issue=1-2 |pages=119–22 |year=1994 |pmid=7898453 |doi=10.1007/BF00928452 ]

ADP-ribose can also be transferred to proteins in long branched chains, in a reaction called poly(ADP-ribosyl)ation.cite journal |author=Diefenbach J, Bürkle A |title=Introduction to poly(ADP-ribose) metabolism |journal=Cell. Mol. Life Sci. |volume=62 |issue=7-8 |pages=721–30 |year=2005 |pmid=15868397 |doi=10.1007/s00018-004-4503-3] This protein modification is carried out by the poly ADP-ribose polymerases (PARPs) which are found in most eukaryotes, but not prokaryotes or yeast.cite journal |author=Burkle A |title=Poly(ADP-ribose). The most elaborate metabolite of NAD+ |journal=FEBS J. |volume=272 |issue=18 |pages=4576–89 |year=2005 |pmid=16156780 |doi=10.1111/j.1742-4658.2005.04864.x] 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.

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. [cite journal |author=De Haan L, Hirst TR |title=Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review) |journal=Mol. Membr. Biol. |volume=21 |issue=2 |pages=77–92 |year=2004 |pmid=15204437 |doi=10.1080/09687680410001663267]

ee also

*Histone code
*Cell signaling

References