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Family-wide analysis of poly(ADP-ribose) polymerase activity

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Vyas, Sejal, Matic, Ivan, Uchima, Lilen, Rood, Jenny, Zaja, Roko, Hay, Ronald T., Ahel, Ivan, Chang, Paul·2014·Nature Communications
DOI 10.1038/ncomms5426
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Abstract

The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD+ as substrate. Based on the composition of three NAD+ coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. In addition, we identify cysteine as a novel amino-acid target for ADP-ribosylation on PARPs. The poly(ADP-ribose) polymerase family of enzymes control many aspects of cellular signalling by covalently modifying proteins with either poly- or mono-(ADP-ribose). Vyas et al.catalogue the catalytic specificity of this family, and reveal that the majority of these enzymes generate only mono(ADP-ribose).

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  1. Ame, J. C., Spenlehauer, C. & de Murcia, G. The PARP superfamily. Bioessays 26, 882–893 (2004). · DOI · Paper page
  2. Ha, G. H. et al. Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation. Cell Death Differ. 19, 321–332 (2012). · DOI
  3. Chang, P., Coughlin, M. & Mitchison, T. J. Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function. Nat. Cell. Biol. 7, 1133–1139 (2005). · DOI · Paper page
  4. Chang, P., Coughlin, M. & Mitchison, T. J. Interaction between Poly(ADP-ribose) and NuMA contributes to mitotic spindle pole assembly. Mol. Biol. Cell. 20, 4575–4585 (2009). · DOI
  5. Chang, P., Jacobson, M. K. & Mitchison, T. J. Poly(ADP-ribose) is required for spindle assembly and structure. Nature 432, 645–649 (2004). · DOI · Paper page
  6. Ozaki, Y. et al. Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation. Mol. Cell 47, 694–706 (2012). · DOI
  7. Ji, Y. & Tulin, A. V. The roles of PARP1 in gene control and cell differentiation. Curr. Opin. Genet. Dev. 20, 512–518 (2010). · DOI
  8. Huang, S.-M. A. et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461, 614–620 (2009). · DOI · Paper page
  9. Zhang, Y. et al. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat. Cell. Biol. 13, 623–629 (2011). · DOI · Paper page
  10. Malanga, M. & Althaus, F. The role of poly(ADP-ribose) in the DNA damage signaling network. Biochem. Cell Biol. 83, 354–364 (2005). · DOI · Paper page
  11. Petesch, S. & Lis, J. Activator-induced spread of poly(ADP-ribose) polymerase promotes nucleosome loss at Hsp70. Mol. Cell 45, 64–74 (2012). · DOI
  12. Di Giammartino, D., Shi, Y. & Manley, J. PARP1 represses PAP and inhibits polyadenylation during heat shock. Mol. Cell 49, 7–17 (2013). · DOI
  13. Leung, A. et al. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Mol. Cell 42, 489–499 (2011). · DOI · Paper page
  14. Kleine, H. et al. Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation. Mol. Cell 32, 57–69 (2008). · DOI · Paper page
  15. Alvarez-Gonzalez, R. & Jacobson, M. Characterization of polymers of adenosine diphosphate ribose generated in vitro and in vivo. Biochemistry 26, 3218–3224 (1987). · DOI · Paper page
  16. Pleschke, J., Kleczkowska, H., Strohm, M. & Althaus, F. Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins. J. Biol. Chem. 275, 40974–40980 (2000). · DOI · Paper page
  17. Karras, G. et al. The macro domain is an ADP-ribose binding module. EMBO J. 24, 1911–1920 (2005). · DOI · Paper page
  18. Ahel, I. et al. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature 451, 81–85 (2008). · DOI · Paper page
  19. Wang, Z. et al. Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination. Genes Dev. 26, 235–240 (2012). · DOI · Paper page
  20. Goenka, S. & Boothby, M. Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor. Proc. Natl Acad. Sci. USA 103, 4210–4215 (2006). · DOI
  21. Rouleau, M. et al. A key role for poly(ADP-ribose) polymerase 3 in ectodermal specification and neural crest development. PloS ONE 6, e15834 (2011). · DOI
  22. MacPherson, L. et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation. Nucleic Acids Res. 41, 1604–1621 (2013). · DOI
  23. Verheugd, P. et al. Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10. Nat. Commun. 4, 1683 (2013). · DOI · Paper page
  24. Cho, S. et al. PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. Blood 113, 2416–2425 (2009). · DOI
  25. Barbarulo, A. et al. Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma. Oncogene 32, 4231–4242 (2013). · DOI
  26. Jwa, M. & Chang, P. PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1alpha-mediated unfolded protein response. Nat. Cell. Biol. 14, 1223–1230 (2012). · DOI · Paper page
  27. Vyas, S., Chesarone-Cataldo, M., Todorova, T., Huang, Y. H. & Chang, P. A systematic analysis of the PARP protein family identifies new functions critical for cell physiology. Nat. Commun. 4, 2240 (2013). · DOI · Paper page
  28. Papini, E., Schiavo, G., Sandona, D., Rappuoli, R. & Montecucco, C. Histidine 21 is at the NAD+ binding site of diphtheria toxin. J. Biol. Chem. 264, 12385–12388 (1989). · doi:10.1016/s0021-9258(18)63870-0
  29. Marsischky, G. T., Wilson, B. A. & Collier, R. J. Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins. J. Biol. Chem. 270, 3247–3254 (1995). · DOI · Paper page
  30. Wahlberg, E. et al. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat. Biotechnol. 30, 283–288 (2012). · DOI · Paper page
  31. Ruf, A., Rolli, V., de Murcia, G. & Schulz, G. The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis. J. Mol. Biol. 278, 57–65 (1998). · DOI · Paper page
  32. Han, S. & Tainer, J. A. The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases. Int. J. Med. Microbiol. 291, 523–529 (2002). · doi:10.1078/1438-4221-00162
  33. Otto, H. et al. In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs). BMC genomics 6, 139 (2005). · DOI · Paper page
  34. Tao, Z., Gao, P. & Liu, H.-W. Identification of the ADP-ribosylation sites in the PARP-1 automodification domain: analysis and implications. J. Am. Chem. Soc. 131, 14258–14260 (2009). · DOI
  35. Chapman, J., Gagné, J.-P., Poirier, G. & Goodlett, D. Mapping PARP-1 Auto-ADP-ribosylation sites by liquid chromatography-tandem mass spectrometry. J. Proteome. Res. 12, 1868–1880 (2013). · DOI
  36. Sharifi, R. et al. Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease. EMBO J. 32, 1225–1237 (2013). · DOI · Paper page
  37. Zhang, Y., Wang, J., Ding, M. & Yu, Y. Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome. Nat. Methods 10, 981–984 (2013). · DOI · Paper page
  38. Altmeyer, M., Messner, S., Hassa, P., Fey, M. & Hottiger, M. Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Res. 37, 3723–3738 (2009). · DOI · Paper page
  39. Messner, S. et al. PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res. 38, 6350–6362 (2010). · DOI · Paper page
  40. Smith, S., Giriat, I., Schmitt, A. & de Lange, T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484–1487 (1998). · DOI · Paper page
  41. Amé, J. et al. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J. Biol. Chem. 274, 17860–17868 (1999). · DOI · Paper page
  42. Kickhoefer, V. A. et al. The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J. Cell. Biol. 146, 917–928 (1999). · DOI · Paper page
  43. Cook, B., Dynek, J., Chang, W., Shostak, G. & Smith, S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol. Cell. Biol. 22, 332–342 (2002). · DOI · Paper page
  44. Aguiar, R., Takeyama, K., He, C., Kreinbrink, K. & Shipp, M. B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity. J. Biol. Chem. 280, 33756–33765 (2005). · DOI · Paper page
  45. Loseva, O. et al. PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA. J. Biol. Chem. 285, 8054–8060 (2010). · DOI
  46. Rulten, S. et al. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol. Cell 41, 33–45 (2011). · DOI · Paper page
  47. Di Paola, S., Micaroni, M., Di Tullio, G., Buccione, R. & Di Girolamo, M. PARP16/ARTD15 is a novel endoplasmic-reticulum-associated mono-ADP-ribosyltransferase that interacts with, and modifies karyopherin-ß1. PloS ONE 7, e37352 (2012). · DOI
  48. Slade, D. et al. The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase. Nature 477, 616–620 (2011). · DOI · Paper page
  49. Lindahl, T., Satoh, M., Poirier, G. & Klungland, A. Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem. Sci. 20, 405–411 (1995). · DOI · Paper page
  50. Kerns, J., Emerman, M. & Malik, H. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet. 4, e21 (2008). · DOI
  51. Barkauskaite, E. et al. Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities. Nat. Commun. 4, 2164 (2013). · DOI
  52. Jankevicius, G. et al. A family of macrodomain proteins reverses cellular mono-ADP-ribosylation. Nat. Struct. Mol. Biol. 20, 508–514 (2013). · DOI · Paper page
  53. Rosenthal, F. et al. Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases. Nat. Struct. Mol. Biol. 20, 502–507 (2013). · DOI · Paper page
  54. Chen, D. et al. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J. Biol. Chem. 286, 13261–13271 (2011). · DOI
  55. Cervantes-Laurean, D., Jacobson, E. & Jacobson, M. Preparation of low molecular weight model conjugates for ADP-ribose linkages to protein. Methods Enzymol. 280, 275–287 (1997). · DOI
  56. Bredehorst, R. et al. Two different types of bonds linking single ADP-ribose residues covalently to proteins. Quantification in eukaryotic cells. Eur. J. Biochem. 92, 129–135 (1978). · doi:10.1111/j.1432-1033.1978.tb12730.x
  57. Simonin, F. et al. The carboxyl-terminal domain of human poly(ADP-ribose) polymerase. Overproduction in Escherichia coli, large scale purification, and characterization. J. Biol. Chem. 268, 13454–13461 (1993). · DOI
  58. Augustin, A. et al. PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression. J. Cell. Sci. 116, 1551–1562 (2003). · DOI
  59. Hatakeyama, K., Nemoto, Y., Ueda, K. & Hayaishi, O. Purification and characterization of poly(ADP-ribose) glycohydrolase. Different modes of action on large and small poly(ADP-ribose). J. Biol. Chem. 261, 14902–14911 (1986). · DOI · Paper page
  60. Lehtio, L. et al. Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. J. Med. Chem. 52, 3108–3111 (2009). · DOI
  61. Steffen, J. D., Brody, J. R., Armen, R. S. & Pascal, J. M. Structural implications for selective targeting of PARPs. Front. Oncol. 3, 301 (2013). · DOI
  62. Jacobson, E., Cervantes-Laurean, D. & Jacobson, M. Glycation of proteins by ADP-ribose. Mol. Cell. Biochem. 138, 207–212 (1994). · DOI
  63. Citarelli, M., Teotia, S. & Lamb, R. Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes. BMC Evol. Biol. 10, 308 (2010). · DOI
  64. Forst, A. et al. Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains. Structure 21, 462–475 (2013). · DOI
  65. Kanai, M. et al. Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Mol. Cell. Biol. 23, 2451–2462 (2003). · DOI
  66. Dunstan, M. et al. Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase. Nat. Commun. 3, 878 (2012). · DOI
  67. Matic, I., Ahel, I. & Hay, R. Reanalysis of phosphoproteomics data uncovers ADP-ribosylation sites. Nat. Methods. 9, 771–772 (2012). · DOI

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Metadata

Authors
Vyas, S., Matic, I., Uchima, L., Rood, J., Zaja, R., Hay, R. T., Ahel, I., & Chang, P.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2014-07-21
Volume
5
Issue
1
Pages
4426-4426
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms5426
OpenAlex
W1575178924
Cited by
497
References
2
FWCI
14.07
Type
journal article
Language
en
Open access
bronze
Licence

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Vyas, S., Matic, I., Uchima, L., Rood, J., Zaja, R., Hay, R. T., Ahel, I., & Chang, P. (2014). Family-wide analysis of poly(ADP-ribose) polymerase activity. Nature Communications. https://doi.org/10.1038/ncomms5426

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