Skip to main content
SpringerLink
Log in

ADP-Ribosyl-Acceptor Hydrolase Activities Catalyzed by the ARH Family of Proteins

  • Protocol
  • First Online:
ADP-ribosylation and NAD+ Utilizing Enzymes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1813))

Abstract

The ARH family of ADP-ribosyl-acceptor hydrolases is composed of three 39-kDa proteins (ARH1, 2, and 3), which hydrolyze specific ADP-ribosylated substrates. ARH1 hydrolyzes mono(ADP-ribosyl)ated arginine, which results from actions of cholera toxin and other nicotinamide adenine dinucleotide (NAD+):arginine ADP-ribosyl-transferases, while ARH3 hydrolyzes poly(ADP-ribose) and O-acetyl-ADP-ribose, resulting from the action of poly(ADP-ribose) polymerases and sirtuins, respectively. ARH2 has not been reported to have enzymatic activity, because of differences in the catalytic domain. Thus, the substrate specificities of ARH1 and ARH3 proteins result in unique cellular functions. In this chapter, we introduce several methods to monitor the activities of the ARH family members.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Verheugd P, Butepage M, Eckei L, Luscher B (2016) Players in ADP-ribosylation: readers and erasers. Curr Protein Pept Sci 17(7):654–667

    Article  CAS  PubMed  Google Scholar 

  2. Palazzo L, Mikoc A, Ahel I (2017) ADP-ribosylation: new facets of an ancient modification. FEBS J 284:2932. https://doi.org/10.1111/febs.14078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Okazaki IJ, Moss J (1996) Mono-ADP-ribosylation: a reversible posttranslational modification of proteins. Adv Pharmacol 35:247–280

    Article  CAS  PubMed  Google Scholar 

  4. Corda D, Di Girolamo M (2003) Functional aspects of protein mono-ADP-ribosylation. EMBO J 22(9):1953–1958. https://doi.org/10.1093/emboj/cdg209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bütepage M, Eckei L, Verheugd P, Luscher B (2015) Intracellular mono-ADP-ribosylation in signaling and disease. Cell 4(4):569–595. https://doi.org/10.3390/cells4040569

    Article  CAS  Google Scholar 

  6. Ogata N, Ueda K, Kagamiyama H, Hayaishi O (1980) ADP-ribosylation of histone H1. Identification of glutamic acid residues 2, 14, and the COOH-terminal lysine residue as modification sites. J Biol Chem 255(16):7616–7620

    CAS  PubMed  Google Scholar 

  7. Altmeyer M, Messner S, Hassa PO, Fey M, Hottiger MO (2009) Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Res 37(11):3723–3738. https://doi.org/10.1093/nar/gkp229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang Y, Wang J, Ding M, Yu Y (2013) Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome. Nat Methods 10(10):981–984. https://doi.org/10.1038/nmeth.2603

    Article  CAS  PubMed  Google Scholar 

  9. Leidecker O, Bonfiglio JJ, Colby T, Zhang Q, Atanassov I, Zaja R, Palazzo L, Stockum A, Ahel I, Matic I (2016) Serine is a new target residue for endogenous ADP-ribosylation on histones. Nat Chem Biol 12(12):998–1000. https://doi.org/10.1038/nchembio.2180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Iglewski BH, Kabat D (1975) NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc Natl Acad Sci U S A 72(6):2284–2288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pappenheimer AM Jr (1977) Diphtheria toxin. Annu Rev Biochem 46:69–94. https://doi.org/10.1146/annurev.bi.46.070177.000441

    Article  CAS  PubMed  Google Scholar 

  12. Cassel D, Pfeuffer T (1978) Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc Natl Acad Sci U S A 75(6):2669–2673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tamura M, Nogimori K, Murai S, Yajima M, Ito K, Katada T, Ui M, Ishii S (1982) Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry 21(22):5516–5522

    Article  CAS  PubMed  Google Scholar 

  14. Vyas S, Chesarone-Cataldo M, Todorova T, Huang YH, Chang P (2013) A systematic analysis of the PARP protein family identifies new functions critical for cell physiology. Nat Commun 4:2240. https://doi.org/10.1038/ncomms3240

    Article  CAS  PubMed  Google Scholar 

  15. Bock FJ, Chang P (2016) New directions in poly(ADP-ribose) polymerase biology. FEBS J 283(22):4017–4031. https://doi.org/10.1111/febs.13737

    Article  CAS  PubMed  Google Scholar 

  16. Gupte R, Liu Z, Kraus WL (2017) PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes. Genes Dev 31(2):101–126. https://doi.org/10.1101/gad.291518.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Borra MT, O'Neill FJ, Jackson MD, Marshall B, Verdin E, Foltz KR, Denu JM (2002) Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases. J Biol Chem 277(15):12632–12641. https://doi.org/10.1074/jbc.M111830200

    Article  CAS  PubMed  Google Scholar 

  18. Liou GG, Tanny JC, Kruger RG, Walz T, Moazed D (2005) Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation. Cell 121(4):515–527. https://doi.org/10.1016/j.cell.2005.03.035

    Article  CAS  PubMed  Google Scholar 

  19. Grubisha O, Rafty LA, Takanishi CL, Xu X, Tong L, Perraud AL, Scharenberg AM, Denu JM (2006) Metabolite of SIR2 reaction modulates TRPM2 ion channel. J Biol Chem 281(20):14057–14065. https://doi.org/10.1074/jbc.M513741200

    Article  CAS  PubMed  Google Scholar 

  20. Moss J, Jacobson MK, Stanley SJ (1985) Reversibility of arginine-specific mono(ADP-ribosyl)ation: identification in erythrocytes of an ADP-ribose-L-arginine cleavage enzyme. Proc Natl Acad Sci U S A 82(17):5603–5607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Oka S, Kato J, Moss J (2006) Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J Biol Chem 281(2):705–713. https://doi.org/10.1074/jbc.M510290200

    Article  CAS  PubMed  Google Scholar 

  22. Mashimo M, Kato J, Moss J (2014) Structure and function of the ARH family of ADP-ribosyl-acceptor hydrolases. DNA Repair (Amst) 23:88–94. https://doi.org/10.1016/j.dnarep.2014.03.005

    Article  CAS  Google Scholar 

  23. Konczalik P, Moss J (1999) Identification of critical, conserved vicinal aspartate residues in mammalian and bacterial ADP-ribosylarginine hydrolases. J Biol Chem 274(24):16736–16740

    Article  CAS  PubMed  Google Scholar 

  24. Ono T, Kasamatsu A, Oka S, Moss J (2006) The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases. Proc Natl Acad Sci U S A 103(45):16687–16691. https://doi.org/10.1073/pnas.0607911103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Moss J, Tsai SC, Adamik R, Chen HC, Stanley SJ (1988) Purification and characterization of ADP-ribosylarginine hydrolase from Turkey erythrocytes. Biochemistry 27(15):5819–5823

    Article  CAS  PubMed  Google Scholar 

  26. Moss J, Balducci E, Cavanaugh E, Kim HJ, Konczalik P, Lesma EA, Okazaki IJ, Park M, Shoemaker M, Stevens LA, Zolkiewska A (1999) Characterization of NAD:arginine ADP-ribosyltransferases. Mol Cell Biochem 193(1–2):109–113

    Article  CAS  PubMed  Google Scholar 

  27. Freissmuth M, Gilman AG (1989) Mutations of GS alpha designed to alter the reactivity of the protein with bacterial toxins. Substitutions at ARG187 result in loss of GTPase activity. J Biol Chem 264(36):21907–21914

    CAS  PubMed  Google Scholar 

  28. Gill DM, Meren R (1978) ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A 75(7):3050–3054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kahn RA, Gilman AG (1984) Purification of a protein cofactor required for ADP-ribosylation of the stimulatory regulatory component of adenylate cyclase by cholera toxin. J Biol Chem 259(10):6228–6234

    CAS  PubMed  Google Scholar 

  30. Kahn RA, Gilman AG (1986) The protein cofactor necessary for ADP-ribosylation of Gs by cholera toxin is itself a GTP binding protein. J Biol Chem 261(17):7906–7911

    CAS  PubMed  Google Scholar 

  31. Kato J, Zhu J, Liu C, Moss J (2007) Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient mice. Mol Cell Biol 27(15):5534–5543. https://doi.org/10.1128/MCB.00302-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kato J, Zhu J, Liu C, Stylianou M, Hoffmann V, Lizak MJ, Glasgow CG, Moss J (2011) ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis. Cancer Res 71(15):5327–5335. https://doi.org/10.1158/0008-5472.CAN-10-0733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kato J, Vekhter D, Heath J, Zhu J, Barbieri JT, Moss J (2015) Mutations of the functional ARH1 allele in tumors from ARH1 heterozygous mice and cells affect ARH1 catalytic activity, cell proliferation and tumorigenesis. Oncogene 4:e151. https://doi.org/10.1038/oncsis.2015.5

    Article  CAS  Google Scholar 

  34. Kasamatsu A, Nakao M, Smith BC, Comstock LR, Ono T, Kato J, Denu JM, Moss J (2011) Hydrolysis of O-acetyl-ADP-ribose isomers by ADP-ribosylhydrolase 3. J Biol Chem 286(24):21110–21117. https://doi.org/10.1074/jbc.M111.237636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mashimo M, Kato J, Moss J (2013) ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress. Proc Natl Acad Sci U S A 110(47):18964–18969. https://doi.org/10.1073/pnas.1312783110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fontana P, Bonfiglio JJ, Palazzo L, Bartlett E, Matic I, Ahel I (2017) Serine ADP-ribosylation reversal by the hydrolase ARH3. elife 6. https://doi.org/10.7554/eLife.28533

  37. Mashimo M, Moss J (2016) Functional role of ADP-Ribosyl-acceptor hydrolase 3 in poly(ADP-ribose) polymerase-1 response to oxidative stress. Curr Protein Pept Sci 17(7):633–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297(5579):259–263. https://doi.org/10.1126/science.1072221

    Article  CAS  PubMed  Google Scholar 

  39. Andrabi SA, Kang HC, Haince JF, Lee YI, Zhang J, Chi Z, West AB, Koehler RC, Poirier GG, Dawson TM, Dawson VL (2011) Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med 17(6):692–699. https://doi.org/10.1038/nm.2387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee Y, Karuppagounder SS, Shin JH, Lee YI, Ko HS, Swing D, Jiang H, Kang SU, Lee BD, Kang HC, Kim D, Tessarollo L, Dawson VL, Dawson TM (2013) Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss. Nat Neurosci 16(10):1392–1400. https://doi.org/10.1038/nn.3500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang Y, An R, Umanah GK, Park H, Nambiar K, Eacker SM, Kim B, Bao L, Harraz MM, Chang C, Chen R, Wang JE, Kam TI, Jeong JS, Xie Z, Neifert S, Qian J, Andrabi SA, Blackshaw S, Zhu H, Song H, Ming GL, Dawson VL, Dawson TM (2016) A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1. Science 354(6308):aad6872. https://doi.org/10.1126/science.aad6872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Andrabi SA, Umanah GK, Chang C, Stevens DA, Karuppagounder SS, Gagne JP, Poirier GG, Dawson VL, Dawson TM (2014) Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis. Proc Natl Acad Sci U S A 111(28):10209–10214. https://doi.org/10.1073/pnas.1405158111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Niere M, Mashimo M, Agledal L, Dolle C, Kasamatsu A, Kato J, Moss J, Ziegler M (2012) ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase (PARG) isoforms, is responsible for degradation of mitochondrial matrix-associated poly(ADP-ribose). J Biol Chem 287(20):16088–16102. https://doi.org/10.1074/jbc.M112.349183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Parihar P, Solanki I, Mansuri ML, Parihar MS (2015) Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases. Exp Gerontol 61:130–141. https://doi.org/10.1016/j.exger.2014.12.004

    Article  CAS  PubMed  Google Scholar 

  45. Osborne B, Bentley NL, Montgomery MK, Turner N (2016) The role of mitochondrial sirtuins in health and disease. Free Radic Biol Med 100:164–174. https://doi.org/10.1016/j.freeradbiomed.2016.04.197

    Article  CAS  PubMed  Google Scholar 

  46. Alvarez-Gonzalez R, Juarez-Salinas H, Jacobson EL, Jacobson MK (1983) Evaluation of immobilized boronates for studies of adenine and pyridine nucleotide metabolism. Anal Biochem 135(1):69–77

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

Funding: The study was funded by the Intramural Research Program, NIH, NHLBI.

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Department of Pharmacology, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan

    Masato Mashimo

  2. Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Joel Moss

Authors
  1. Masato Mashimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel Moss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joel Moss .

Editor information

Editors and Affiliations

  1. Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Paul Chang

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Mashimo, M., Moss, J. (2018). ADP-Ribosyl-Acceptor Hydrolase Activities Catalyzed by the ARH Family of Proteins. In: Chang, P. (eds) ADP-ribosylation and NAD+ Utilizing Enzymes. Methods in Molecular Biology, vol 1813. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-8588-3_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8588-3_12

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-8587-6

  • Online ISBN: 978-1-4939-8588-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation