Pokeweed antiviral protein, a ribosome inactivating protein: Activity, inhibition and prospects

Toxins

Volumn 7, Issue 2, 2015, Pages 274-298

  Domashevskiy, Artem V ^a   Goss, Dixie J ^b  

^a JOHN JAY COLLEGE OF CRIMINAL JUSTICE   (United States)

^b CITY UNIVERSITY OF NEW YORK   (United States)

Author keywords

Immunotoxin; Pokeweed antiviral protein; Ribosome inactivating protein; Sarcin ricin loop; Virus genome linked protein

Indexed keywords

ALPHA SARCIN; GLYCOPEPTIDASE; IMMUNOTOXIN; INITIATION FACTOR; ISOPROTEIN; MESSENGER RNA; POKEWEED ANTIVIRUS PROTEIN; RIBOSOME INACTIVATING PROTEIN; RIBOSOME RNA; RICIN; ALPHA-SARCIN; CAPPED RNA; FUNGAL PROTEIN; PLANT RNA; RIBONUCLEASE; RIBOSOME INACTIVATING PROTEIN 1; VIRUS RNA;

ANTIVIRAL ACTIVITY; CANCER THERAPY; CRYSTAL STRUCTURE; ENZYME ACTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; NONHUMAN; PLANT DEFENSE; POKEWEED; POTYVIRUS; PROTEIN NUCLEIC ACID INTERACTION; PROTEIN SYNTHESIS INHIBITION; REVIEW; RNA CAPPING; RNA STRUCTURE; VIRUS GENOME; ANIMAL; BINDING SITE; CHEMISTRY; GENETICS; METABOLISM; RIBOSOME;

PHYTOLACCA AMERICANA; PHYTOLACCACEAE;

ANIMALS; BINDING SITES; ENDORIBONUCLEASES; FUNGAL PROTEINS; GENOME, VIRAL; HUMANS; PROTEIN ISOFORMS; RIBOSOME INACTIVATING PROTEINS, TYPE 1; RIBOSOMES; RICIN; RNA CAPS; RNA, PLANT; RNA, RIBOSOMAL; RNA, VIRAL;

EID: 84923197833     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins7020274     Document Type: Review

References (184)

1. Olsnes, S. The history of ricin, abrin and related toxins. Toxicon 2004, 44, 361–370.
2. Christopher, G.W.; Cieslak, T.J.; Pavlin, J.A.; Eitzen, E.M. Biological warfare. A historical perspective. JAMA 1997, 278, 412–417.
3. Knight, B. Ricin-A potent homicidal poison. Br. Med. J. 1979, 1, 350–351.
4. Wiener, S.L. Strategies for the prevention of a successful biological warfare aerosol attack. Mil. Med. 1996, 161, 251–256.
5. Lodge, J.K.; Kaniewski, W.K.; Tumer, N.E. Broad-spectrum virus resistance in transgenic plants expressing pokeweed antiviral protein. Proc. Natl. Acad. Sci. USA 1993, 90, 7089–7093.
6. Jach, G.; Gornhardt, B.; Mundy, J.; Logemann, J.; Pinsdorf, E.; Leah, R.; Schell, J.; Maas, C. Enhanced quantitative resistance against fungal disease by combinatorial expression of different barley antifungal proteins in transgenic tobacco. Plant J. 1995, 8, 97–109.
7. Frankel, A.E.; FitzGerald, D.; Siegall, C.; Press, O.W. Advances in immunotoxin biology and therapy: A summary of the fourth international symposium on immunotoxins. Cancer Res. 1996, 56, 926–932.
8. Kreitman, R.J. Immunotoxins in cancer therapy. Curr. Opin. Immunol. 1999, 11, 570–578.
9. Pastan, I.; FitzGerald, D. Recombinant toxins for cancer treatment. Science 1991, 254, 1173–1177.
10. Christie, A. House of lurking death. In Partners in Crime; Dodd, Mead and Company: New York, NY, USA, 1929.
11. Peumans, W.J.; Hao, Q.; van Damme, E.J. Ribosome-inactivating proteins from plants: More than RNA N-glycosidases? FASEB J. 2001, 15, 1493–1506.
12. Irvin, J.D. Purification and partial characterization of the antiviral protein from Phytolacca americana which inhibits eukaryotic protein synthesis. Arch. Biochem. Biophys. 1975, 169, 522–528.
13. Fordham-Skelton, A.P.; Taylor, P.N.; Hartley, M.R.; Croy, R.R. Characterisation of saporin genes: in vitro expression and ribosome inactivation. Mol. Gen. Genet. 1991, 229, 460–466.
14. The Arabidopsis Genome Initiative. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 2000, 408, 796–815.
15. Ready, M.P.; Brown, D.T.; Robertus, J.D. Extracellular localization of pokeweed antiviral protein. Proc. Natl. Acad. Sci. USA 1986, 83, 5053–5056.
16. Bonness, M.S.; Ready, M.P.; Irvin, J.D.; Mabry, T.J. Pokeweed antiviral protein inactivates pokeweed ribosomes; implications for the antiviral mechanism. Plant J. 1994, 5, 173–183.
17. Domashevskiy, A.V. Turnip Mosaic Virus Genome-Linked Protein (VPg) Inhibits Pokeweed Antiviral Protein (PAP)-Mediated Depurination of RNA. Ph.D. Thesis, Graduate Center and Hunter College, City University of New York, New York, NY, USA, May 2012.
18. Ehrlich, P. Experimentelle Untersuchungenüber Immunität I. Ueber Ricin. Dtsch. Med. Wochenschr. 1891, 17, 976–979. (In German)
19. Ehrlich, P. Experimentelle Untersuchungenüber Immunität I. Ueber Abrin. Dtsch. Med. Wochenschr. 1891, 17, 1218–1219. (In German)
20. Lin, J.Y.; Liu, K.; Chen, C.C.; Tung, T.C. Effect of crystalline ricin on the biosynthesis of protein, RNA, and DNA in experimental tumor cells. Cancer Res. 1971, 31, 921–924.
21. Montanaro, L.; Sperti, S.; Stirpe, F. Inhibition by ricin of protein synthesis in vitro. Ribosomes as the target of the toxin. Biochem. J. 1973, 136, 677–683.
22. Obrig, T.G.; Irvin, J.D.; Hardesty, B. The effect of an antiviral peptide on the ribosomal reactions of the peptide elongation enzymes, EF-I and EF-II. Arch. Biochem. Biophys. 1973, 155, 278–289.
23. Mundy, J.; Leah, R.; Boston, R.; Endo, Y.; Stirpe, F. Genes encoding ribosome-inactivating proteins. Plant Mol. Biol. Rep. 1994, 12, S60–S62.
24. Girbes, T.; Ferreras, J.M.; Arias, F.J.; Stirpe, F. Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev. Med. Chem. 2004, 4, 461–476.
25. Barbieri, L.; Battelli, M.G.; Stirpe, F. Ribosome-inactivating proteins from plants. Biochim. Biophys. Acta 1993, 1154, 237–282.
26. Husain, J.; Tickle, I.J.; Wood, S.P. Crystal structure of momordin, a type I ribosome inactivating protein from the seeds of Momordica charantia. FEBS Lett. 1994, 342, 154–158.
27. Mlsna, D.; Monzingo, A.F.; Katzin, B.J.; Ernst, S.; Robertus, J.D. Structure of recombinant ricin A chain at 2.3 A. Protein Sci. 1993, 2, 429–435.
28. Monzingo, A.F.; Robertus, J.D. X-ray analysis of substrate analogs in the ricin A-chain active site. J. Mol. Biol. 1992, 227, 1136–1145.
29. Savino, C.; Federici, L.; Ippoliti, R.; Lendaro, E.; Tsernoglou, D. The crystal structure of saporin SO6 from Saponaria officinalis and its interaction with the ribosome. FEBS Lett. 2000, 470, 239–243.
30. Monzingo, A.F.; Collins, E.J.; Ernst, S.R.; Irvin, J.D.; Robertus, J.D. The 2.5 A structure of pokeweed antiviral protein. J. Mol. Biol. 1993, 233, 705–715.
31. Zhou, K.; Fu, Z.; Chen, M.; Lin, Y.; Pan, K. Structure of trichosanthin at 1.88 A resolution. Proteins 1994, 19, 4–13.
32. Hosur, M.V.; Nair, B.; Satyamurthy, P.; Misquith, S.; Surolia, A.; Kannan, K.K. X-ray structure of gelonin at 1.8 A resolution. J. Mol. Biol. 1995, 250, 368–380.
33. Ferreras, J.M.; Barbieri, L.; Girbes, T.; Battelli, M.G.; Rojo, M.A.; Arias, F.J.; Rocher, M.A.; Soriano, F.; Mendez, E.; Stirpe, F. Distribution and properties of major ribosome-inactivating proteins (28 S rRNA N-glycosidases) of the plant Saponaria officinalis L. (Caryophyllaceae). Biochim. Biophys. Acta. 1993, 1216, 31–42.
34. Kurinov, I.V.; Myers, D.E.; Irvin, J.D.; Uckun, F.M. X-ray crystallographic analysis of the structural basis for the interactions of pokeweed antiviral protein with its active site inhibitor and ribosomal RNA substrate analogs. Protein Sci. 1999, 8, 1765–1772.
35. Olsnes, S.; Pihl, A. Isolation and properties of abrin: A toxic protein inhibiting protein synthesis. Evidence for different biological functions of its two constituent-peptide chains. Eur. J. Biochem. 1973, 35, 179–185.
36. Olsnes, S.; Pihl, A. Chimeric toxins. Pharmacol. Ther. 1981, 15, 355–381.
37. Stirpe, F.; Gasperi-Campani, A.; Barbieri, L.; Lorenzoni, E.; Montanaro, L.; Sperti, S.; Bonetti, E. Inhibition of protein synthesis by modeccin, the toxin of Modecca digitata. FEBS Lett. 1977, 85, 65–67.
38. Sandvig, K.; Olsnes, S.; Pihl, A. Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J. Biol. Chem. 1976, 251, 3977–3984.
39. Olsnes, S.; Sandvig, K. How protein toxins enter and kill cells. Cancer Treat. Res. 1988, 37, 39–73.
40. Steeves, R.M.; Denton, M.E.; Barnard, F.C.; Henry, A.; Lambert, J.M. Identification of three oligosaccharide binding sites in ricin. Biochemistry 1999, 38, 11677–11685.
41. Van Deurs, B.; Tonnessen, T.I.; Petersen, O.W.; Sandvig, K.; Olsnes, S. Routing of internalized ricin and ricin conjugates to the Golgi complex. J. Cell Biol. 1986, 102, 37–47.
42. Beaumelle, B.; Alami, M.; Hopkins, C.R. ATP-dependent translocation of ricin across the membrane of purified endosomes. J. Biol. Chem. 1993, 268, 23661–23669.
43. Sandvig, K.; van Deurs, B. Endocytosis and intracellular sorting of ricin and Shiga toxin. FEBS Lett. 1994, 346, 99–102.
44. Hazes, B.; Read, R.J. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 1997, 36, 11051–11054.
45. Lord, J.M.; Roberts, L.M. Toxin entry: Retrograde transport through the secretory pathway. J. Cell Biol. 1998, 140, 733–736.
46. Sandvig, K.; van Deurs, B. Endocytosis and intracellular transport of ricin: Recent discoveries. FEBS Lett. 1999, 452, 67–70.
47. Kaloyanova, D.; Kyurkchiev, S.; Xu, J.; Abouhaidar, M.; Ivanov, I. Mouse monoclonal antibodies against Phytolacca americana antiviral protein PAP I. Hybridoma 1999, 18, 367–370.
48. Parikh, B.A.; Baykal, U.; Di, R.; Tumer, N.E. Evidence for retro-translocation of pokeweed antiviral protein from endoplasmic reticulum into cytosol and separation of its activity on ribosomes from its activity on capped RNA. Biochemistry 2005, 44, 2478–2490.
49. Bass, H.W.; Webster, C.; O’Brian, G.R.; Roberts, J.K.; Boston, R.S. A maize ribosome-inactivating protein is controlled by the transcriptional activator Opaque-2. Plant Cell 1992, 4, 225–234.
50. Chaudhry, B.; Muller-Uri, F.; Cameron-Mills, V.; Gough, S.; Simpson, D.; Skriver, K.; Mundy, J. The barley 60 kDa jasmonate-induced protein (JIP60) is a novel ribosome-inactivating protein. Plant J. 1994, 6, 815–824.
51. Reinbothe, S.; Reinbothe, C.; Lehmann, J.; Becker, W.; Apel, K.; Parthier, B. JIP60, a methyl jasmonate-induced ribosome-inactivating protein involved in plant stress reactions. Proc. Natl. Acad. Sci. USA 1994, 91, 7012–7016.
52. Walsh, T.A.; Morgan, A.E.; Hey, T.D. Characterization and molecular cloning of a proenzyme form of a ribosome-inactivating protein from maize. Novel mechanism of proenzyme activation by proteolytic removal of a 2.8-kilodalton internal peptide segment. J. Biol. Chem. 1991, 266, 23422–23427.
53. Jimenez, A.; Vazquez, D. Plant and fungal protein and glycoprotein toxins inhibiting eukaryote protein synthesis. Annu. Rev. Microbiol. 1985, 39, 649–672.
54. Stirpe, F.; Barbieri, L. Ribosome-inactivating proteins up to date. FEBS Lett. 1986, 195, 1–8.
55. Barbieri, L.; Valbonesi, P.; Bondioli, M.; Alvarez, M.L.; Dal Monte, P.; Landini, M.P.; Stirpe, F. Adenine glycosylase activity in mammalian tissues: An equivalent of ribosome-inactivating proteins. FEBS Lett. 2001, 505, 196–197.
56. Stirpe, F.; Barbieri, L.; Gorini, P.; Valbonesi, P.; Bolognesi, A.; Polito, L. Activities associated with the presence of ribosome-inactivating proteins increase in senescent and stressed leaves. FEBS Lett. 1996, 382, 309–312.
57. Girbés, T.; de Torre, C.; Iglesias, R.; Ferreras, J.M.; Mendéz, E. RIP for viruses. Nature 1996, 379, 777–778.
58. Rippmann, J.F.; Michalowski, C.B.; Nelson, D.E.; Bohnert, H.J. Induction of a ribosome-inactivating protein upon environmental stress. Plant Mol. Biol. 1997, 35, 701–709.
59. Melton-Celsa, A.R. Shiga toxin (Stx) classification, structure, and function. Microbiol. Spectr. 2014, 9, 1–13.
60. Russo, L.M.; Melton-Celsa, A.R.; Smith, M.J.; O’Brien, A.D. Comparisons of native shiga Toxins (Stxs) Type 1 and 2 with chimeric toxins indicate that the source of the binding subunit dictates degree of toxicity. PLoS One 2014, 9, doi:10.1371/journal.pone.0093463.
61. Brown, J.E.; Ussery, M.A.; Leppla, S.H.; Rothman, S.W. Inhibition of protein synthesis by Shiga toxin: Activation of the toxin and inhibition of peptide elongation. FEBS Lett. 1980, 117, 84–88.
62. Sandvig, K.; van Deurs, B. Transport of protein toxins into cells: Pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett. 2002, 529, 49–53.
63. Bergan, J.; Dyve Lingelem, A.B.; Simm, R.; Skotland, T.; Sandvig, K. Shiga toxins. Toxicon 2012, 60, 1085–1107.
64. Lam, S.K.; Ng, T.B. First simultaneous isolation of a ribosome inactivating protein and an antifungal protein from a mushroom (Lyophyllum shimeji) together with evidence for synergism of their antifungal effects. Arch. Biochem. Biophys. 2001, 393, 271–280.
65. Lam, S.K.; Ng, T.B. Hypsin, a novel thermostable ribosome-inactivating protein with antifungal and antiproliferative activities from fruiting bodies of the edible mushroom Hypsizigus marmoreus. Biochem. Biophys. Res. Commun. 2001, 285, 1071–1075.
66. Wang, H.; Ng, T.B. Isolation and characterization of velutin, a novel low-molecular-weight ribosome-inactivating protein from winter mushroom (Flammulina velutipes) fruiting bodies. Life Sci. 2001, 68, 2151–2158.
67. Yao, Q.Z.; Yu, M.M.; Ooi, L.S.; Ng, T.B.; Chang, S.T.; Sun, S.S.; Ooi, V.E. Isolation and Characterization of a Type 1 Ribosome-Inactivating Protein from Fruiting Bodies of the Edible Mushroom (Volvariella volvacea). J. Agric. Food Chem. 1998, 46, 788–792.
68. Liu, R.S.; Yang, J.H.; Liu, W.Y. Isolation and enzymatic characterization of lamjapin, the first ribosome-inactivating protein from cryptogamic algal plant (Laminaria japonica A). Eur. J. Biochem. 2002, 269, 4746–4752.
69. Lin, Q.; Chen, Z.C.; Antoniw, J.F.; White, R.F. Isolation and characterization of a cDNA clone encoding the anti-viral protein from Phytolacca americana. Plant Mol. Biol. 1991, 17, 609–614.
70. Irvin, J.D.; Uckun, F.M. Pokeweed antiviral protein: Ribosome inactivation and therapeutic applications. Pharmacol. Ther. 1992, 55, 279–302.
71. Myers, D.E.; Irvin, J.D.; Smith, R.S.; Kuebelbeck, V.M.; Uckun, F.M. Production of a pokeweed antiviral protein (PAP)-containing immunotoxin, B43-PAP, directed against the CD19 human B lineage lymphoid differentiation antigen in highly purified form for human clinical trials. J. Immunol. Methods 1991, 136, 221–237.
72. Poyet, J.L.; Radom, J.; Hoeveler, A. Isolation and characterization of a cDNA clone encoding the pokeweed antiviral protein II from Phytolacca americana and its expression in E. coli. FEBS Lett. 1994, 347, 268–272.
73. Rajamohan, F.; Engstrom, C.R.; Denton, T.J.; Engen, L.A.; Kourinov, I.; Uckun, F.M. High-level expression and purification of biologically active recombinant pokeweed antiviral protein. Protein Expr. Purif. 1999, 16, 359–368.
74. Poyet, J.L.; Hoeveler, A. cDNA cloning and expression of pokeweed antiviral protein from seeds in Escherichia coli and its inhibition of protein synthesis in vitro. FEBS Lett. 1997, 406, 97–100.
75. Barbieri, L.; Aron, G.M.; Irvin, J.D.; Stirpe, F. Purification and partial characterization of another form of the antiviral protein from the seeds of Phytolacca americana L. (pokeweed). Biochem. J. 1982, 203, 55–59.
76. Honjo, E.; Dong, D.; Motoshima, H.; Watanabe, K. Genomic clones encoding two isoforms of pokeweed antiviral protein in seeds (PAP-S1 and S2) and the N-glycosidase activities of their recombinant proteins on ribosomes and DNA in comparison with other isoforms. J. Biochem. 2002, 131, 225–231.
77. Hartley, M.R.; Lord, J.M. Genetics of ribosome-inactivating proteins. Mini Rev. Med. Chem. 2004, 4, 487–492.
78. Battelli, M.G.; Citores, L.; Buonamici, L.; Ferreras, J.M.; de Benito, F.M.; Stirpe, F.; Girbes, T. Toxicity and cytotoxicity of nigrin b, a two-chain ribosome-inactivating protein from Sambucus nigra: Comparison with ricin. Arch. Toxicol. 1997, 71, 360–364.
79. Duggar, B.M.; Armstrong, J.K. The effect of treating virus of tobacco mosaic with juice of various plants. Ann. Mol. Bot. Gard. 1925, 12, 360–364.
80. Dallal, J.A.; Irvin, J.D. Enzymatic inactivation of eukaryotic ribosomes by the pokeweed antiviral protein. FEBS Lett. 1978, 89, 257–259.
81. Kataoka, J.; Habuka, N.; Matuta, C.; Miyano, M.; Koiwai, A. Isolation and analysis of a genomic clone encoding a pokeweed antiviral protein. Plant Mol. Biol. 1992, 20, 879–886.
82. Chen, Z.C.; Antoniw, J.F.; Hefferon, K.L.; Ivanov, I.G.; Abouhaidar, M.G. Expression of pokeweed (Phytolacca americana) antiviral protein cDNA in Escherichia coli and its antiviral activity. Physiol. Mol. Plant Path. 1993, 42, 237–247.
83. Xu, J.; Meng, A.X.; Hefferon, K.L.; Ivanov, I.G.; Abouhaidar, M.G. Effect of N-terminal deletions on the activity of pokeweed antiviral protein expressed in E. coli. Biochimie 1998, 80, 1069–1076.
84. Ago, H.; Kataoka, J.; Tsuge, H.; Habuka, N.; Inagaki, E.; Noma, M.; Miyano, M. X-ray structure of pokeweed antiviral protein, coded by a new gwnomic clone, at 0.23 nm resolution. A model structure provides a suitable electrostatic field for substrate binding. Eur. J. Biochem. 1994, 225, 369–374.
85. Islam, M.R.; Kung, S.S.; Kimura, Y.; Funatsu, G. N-acetyl-D-glucosamine-asparagine structure in ribosome-inactivating proteins from seeds of Luffa cylindrica and Phytolacca americana. Agric. Biol. Chem. 1991, 55, 1375–1381.
86. Kurinov, I.V.; Uckun, F.M. High resolution X-ray structure of potent anti-HIV pokeweed antiviral protein-III. Biochem. Pharmacol. 2003, 65, 1709–1717.
87. Kurinov, I.V.; Rajamohan, F.; Venkatachalam, T.K.; Uckun, F.M. X-ray crystallographic analysis of the structural basis for the interaction of pokeweed antiviral protein with guanine residues of ribosomal RNA. Protein Sci. 1999, 8, 2399–2405.
88. Rajamohan, F.; Venkatachalam, T.K.; Irvin, J.D.; Uckun, F.M. Pokeweed antiviral protein isoforms PAP-I, PAP-II, and PAP-III depurinate RNA of human immunodeficiency virus (HIV)-1. Biochem. Biophys. Res. Commun. 1999, 260, 453–458.
89. Bolognesi, A.; Barbieri, L.; Abbondanza, A.; Falasca, A.I.; Carnicelli, D.; Battelli, M.G.; Stirpe, F. Purification and properties of new ribosome-inactivating proteins with RNA N-glycosidase activity. Biochim. Biophys. Acta 1990, 1087, 293–302.
90. Park, S.W.; Lawrence, C.B.; Linden, J.C.; Vivanco, J.M. Isolation and characterization of a novel ribosome-inactivating protein from root cultures of pokeweed and its mechanism of secretion from roots. Plant Physiol. 2002, 130, 164–178.
91. Barbieri, L.; Bolognesi, A.; Cenini, P.; Falasca, A.I.; Minghetti, A.; Garofano, L.; Guicciardi, A.; Lappi, D.; Miller, S.P.; Stirpe, F. Ribosome-inactivating proteins from plant cells in culture. Biochem. J. 1989, 257, 801–807.
92. Sperti, S.; Montanaro, L.; Mattioli, A.; Testoni, G. Relationship between elongation factor I- and elongation factor II- dependent guanosine triphosphatase activities of ribosomes. Inhibition of both activities by ricin. Biochem. J. 1975, 148, 447–451.
93. Barbieri, L.; Ferreras, J.M.; Barraco, A.; Ricci, P.; Stirpe, F. Some ribosome-inactivating proteins depurinate ribosomal RNA at multiple sites. Biochem. J. 1992, 286, 1–4.
94. Barbieri, L.; Valbonesi, P.; Bonora, E.; Gorini, P.; Bolognesi, A.; Stirpe, F. Polynucleotide: Adenosine glycosidase activity of ribosome-inactivating proteins: Effect on DNA, RNA and poly(A). Nucleic Acids Res. 1997, 25, 518–522.
95. Endo, Y.; Mitsui, K.; Motizuki, M.; Tsurugi, K. The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins. J. Biol. Chem. 1987, 262, 5908–5912.
96. Gutell, R.R.; Fox, G.E. A compilation of large subunit RNA sequences presented in a structural format. Nucleic Acids Res. 1988, 16, r175–r269.
97. Chen, X.Y.; Link, T.M.; Schramm, V.L. Ricin A-chain: kinetics, mechanism, and RNA stem-loop inhibitors. Biochemistry 1998, 37, 11605–11613.
98. Tanaka, K.S.; Chen, X.Y.; Ichikawa, Y.; Tyler, P.C.; Furneaux, R.H.; Schramm, V.L. Ricin A-chain inhibitors resembling the oxacarbenium ion transition state. Biochemistry 2001, 40, 6845–6851.
99. Mansouri, S.; Nourollahzadeh, E.; Hudak, K.A. Pokeweed antiviral protein depurinates the sarcin/ricin loop of the rRNA prior to binding of aminoacyl-tRNA to the ribosomal A-site. RNA 2006, 12, 1683–1692.
100. Hudak, K.A.; Hammell, A.B.; Yasenchak, J.; Tumer, N.E.; Dinman, J.D. A C-terminal deletion mutant of pokeweed antiviral protein inhibits programmed+1 ribosomal frameshifting and Ty1 retrotransposition without depurinating the sarcin/ricin loop of rRNA. Virology 2001, 279, 292–301.
101. Tumer, N.E.; Parikh, B.A.; Li, P.; Dinman, J.D. The pokeweed antiviral protein specifically inhibits Ty1-directed +1 ribosomal frameshifting and retrotransposition in Saccharomyces cerevisiae. J. Virol. 1998, 72, 1036–1042.
102. Vater, C.A.; Bartle, L.M.; Leszyk, J.D.; Lambert, J.M.; Goldmacher, V.S. Ricin A chain can be chemically cross-linked to the mammalian ribosomal proteins L9 and L10e. J. Biol. Chem. 1995, 270, 12933–12940.
103. Hudak, K.A.; Dinman, J.D.; Tumer, N.E. Pokeweed antiviral protein accesses ribosomes by binding to L3. J. Biol. Chem. 1999, 274, 3859–3864.
104. Di, R.; Tumer, N.E. Expression of a truncated form of ribosomal protein L3 confers resistance to pokeweed antiviral protein and the Fusarium mycotoxin deoxynivalenol. Mol. Plant-Microbe Interact. 2005, 18, 762–770.
105. Endo, Y.; Gluck, A.; Wool, I.G. Ribosomal RNA identity elements for ricin A-chain recognition and catalysis. J. Mol. Biol. 1991, 221, 193–207.
106. Tan, Q.Q.; Dong, D.X.; Yin, X.W.; Sun, J.; Ren, H.J.; Li, R.X. Comparative analysis of depurination catalyzed by ricin A-chain on synthetic 32mer and 25mer oligoribonucleotides mimicking the sarcin/ricin domain of the rat 28S rRNA and E. coli 23S rRNA. J. Biotechnol. 2009, 139, 156–162.
107. Domashevskiy, A.V.; Miyoshi, H.; Goss, D.J. Inhibition of pokeweed antiviral protein (PAP) by turnip mosaic virus genome-linked protein (VPg). J. Biol. Chem. 2012, 287, 29729–29738.
108. Tang, S.; Xie, L.; Hou, F.; Liu, W.Y.; Ruan, K. Non-specific deadenylation and deguanylation of naked RNA catalyzed by ricin under acidic condition. Biochim. Biophys. Acta 2001, 1519, 192–198.
109. Zamboni, M.; Brigotti, M.; Rambelli, F.; Montanaro, L.; Sperti, S. High-pressure-liquid-chromatographic and fluorimetric methods for the determination of adenine released from ribosomes by ricin and gelonin. Biochem. J. 1989, 259, 639–643.
110. Rajamohan, F.; Kurinov, I.V.; Venkatachalam, T.K.; Uckun, F.M. Deguanylation of human immunodeficiency virus (HIV-1) RNA by recombinant pokeweed antiviral protein. Biochem. Biophys. Res. Commun. 1999, 263, 419–424.
111. Uckun, F.M.; Rajamohan, F.; Pendergrass, S.; Ozer, Z.; Waurzyniak, B.; Mao, C. Structure-based design and engineering of a nontoxic recombinant pokeweed antiviral protein with potent anti-human immunodeficiency virus activity. Antimicrob. Agents Chemother. 2003, 47, 1052–1061.
112. Chen, Z.; Antoniw, J.F.; White, R.F. A possible mechanism for the antiviral activity of pokeweed antiviral protein. Physiol. Mol. Plant Path. 1993, 42, 249–258.
113. Ussery, M.A.; Irvin, J.D.; Hardesty, B. Inhibition of poliovirus replication by a plant antiviral peptide. Ann. NY Acad. Sci. 1977, 284, 431–440.
114. Aron, G.M.; Irvin, J.D. Inhibition of herpes simplex virus multiplication by the pokeweed antiviral protein. Antimicrob. Agents Chemother. 1980, 17, 1032–1033.
115. Tomlinson, J.A.; Walker, V.M.; Flewett, T.H.; Barclay, G.R. The inhibition of infection by cucumber mosaic virus and influenza virus by extracts from Phytolacca americana. J. Gen. Virol. 1974, 22, 225–232.
116. Picard, D.; Kao, C.C.; Hudak, K.A. Pokeweed antiviral protein inhibits brome mosaic virus replication in plant cells. J. Biol. Chem. 2005, 280, 20069–20075.
117. Uckun, F.M.; Rustamova, L.; Vassilev, A.O.; Tibbles, H.E.; Petkevich, A.S. CNS activity of Pokeweed anti-viral protein (PAP) in mice infected with lymphocytic choriomeningitis virus (LCMV). BMC Infect. Dis. 2005, 5, 9.
118. Ishag, H.Z.; Li, C.; Huang, L.; Sun, M.X.; Ni, B.; Guo, C.X.; Mao, X. Inhibition of Japanese encephalitis virus infection in vitro and in vivo by pokeweed antiviral protein. Virus Res. 2013, 171, 89–96.
119. Hudak, K.A.; Wang, P.; Tumer, N.E. A novel mechanism for inhibition of translation by pokeweed antiviral protein: Depurination of the capped RNA template. RNA 2000, 6, 369–380.
120. Hudak, K.A.; Bauman, J.D.; Tumer, N.E. Pokeweed antiviral protein binds to the cap structure of eukaryotic mRNA and depurinates the mRNA downstream of the cap. RNA 2002, 8, 1148–1159.
121. Baldwin, A.E.; Khan, M.A.; Tumer, N.E.; Goss, D.J.; Friedland, D.E. Characterization of pokeweed antiviral protein binding to mRNA cap analogs: Competition with nucleotides and enhancement by translation initiation factor iso4G. Biochim. Biophys. Acta 2009, 1789, 109–116.
122. Zoubenko, O.; Hudak, K.; Tumer, N.E. A non-toxic pokeweed antiviral protein mutant inhibits pathogen infection via a novel salicylic acid-independent pathway. Plant Mol. Biol. 2000, 44, 219–229.
123. Vivanco, J.M.; Tumer, N.E. Translation Inhibition of Capped and Uncapped Viral RNAs Mediated by Ribosome-Inactivating Proteins. Phytopathology 2003, 93, 588–595.
124. Wang, M.; Hudak, K.A. A novel interaction of pokeweed antiviral protein with translation initiation factors 4G and iso4G: A potential indirect mechanism to access viral RNAs. Nucleic Acids Res. 2006, 34, 1174–1181.
125. Allen, M.L.; Metz, A.M.; Timmer, R.T.; Rhoads, R.E.; Browning, K.S. Isolation and sequence of the cDNAs encoding the subunits of the isozyme form of wheat protein synthesis initiation factor 4F. J. Biol. Chem. 1992, 267, 23232–23236.
126. Browning, K.S. The plant translational apparatus. Plant Mol. Biol. 1996, 32, 107–144.
127. Cheng, S.; Domashevskiy, A.; Kobilinsky, L. The Effect of Eukaryotic Initiation Factors on the Activity of Pokeweed Antiviral Protein; Society of Toxicology: Reston, VA, USA, 2014.
128. Gallie, D.R.; Walbot, V. RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a poly(A) tail in plant and animal cells. Genes Dev. 1990, 4, 1149–1157.
129. Gallie, D.R.; Kobayashi, M. The role of the 3'-untranslated region of non-polyadenylated plant viral mRNAs in regulating translational efficiency. Gene 1994, 142, 159–165.
130. Williams, S.; Domashevskiy, A.V. Pokeweed antiviral protein binds to structures present in the 3' untranslated regions of viral mRNA. In Proceeding of Annual Biomedical Research Conference for Minority Students, San Antonio, TX, USA, 12–15 November 2014.
131. Domashevskiy, A.V. The 3' Untranslated Regions within Viral RNA Affects Pokeweed Antiviral Protein Antiviral Activity; American Society of Biochemistry and Molecular Biology: Rockville, MD, USA, 2015.
132. Sandvig, K.; van Deurs, B. Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. EMBO J. 2000, 19, 5943–5950.
133. Van Damme, E.J.; Peumans, W.J.; Barre, A.; Rouge, P. Plant lectins: a composite of several distinct families of structurally and evolutionary related proteins with diverse biological roles. Crit. Rev. Plant Sci. 1998, 17, 575–692.
134. Tumer, N.E.; Hudak, K.; Di, R.; Coetzer, C.; Wang, P.; Zoubenko, O. Pokeweed antiviral protein and its applications. Curr. Top Microbiol. Immunol. 1999, 240, 139–158.
135. Dowd, P.F.; Zuo, W.N.; Gillikin, J.W.; Johnson, E.T.; Boston, R.S. Enhanced resistance to Helicoverpa zea in tobacco expressing an activated form of maize ribosome-inactivating protein. J. Agric. Food Chem. 2003, 51, 3568–3574.
136. Wang, P.; Tumer, N.E. Virus resistance mediated by ribosome inactivating proteins. Adv. Virus Res. 2000, 55, 325–355.
137. Craig, H.L.; Alderks, O.H.; Corwin, A.H.; Dieke, S.H.; Karel, C.L. Preparation of toxic ricin. U.S. Patent 3,060,165, 1962.
138. Smallshaw, J.E.; Firan, A.; Fulmer, J.R.; Ruback, S.L.; Ghetie, V.; Vitetta, E.S. A novel recombinant vaccine which protects mice against ricin intoxication. Vaccine 2002, 20, 3422–3427.
139. Mayor, S. UK doctors warned after ricin poison found in police raid. BMJ 2003, 326, 126.
140. Texas actress who sent Obama ricin sentenced to 18 years. Available online: http://www.cnn.com/ 2014/07/16/justice/texas-ricin-actress-sentenced/index.html (accessed on 27 January 2015).
141. Tourlakis, M.E.; Karran, R.A.; Desouza, L.; Siu, K.W.; Hudak, K.A. Homodimerization of pokeweed antiviral protein as a mechanism to limit depurination of pokeweed ribosomes. Mol. Plant Path. 2010, 11, 757–767.
142. Bolognesi, A.; Polito, L. Immunotoxins and other conjugates: Pre-clinical studies. Mini Rev. Med. Chem. 2004, 4, 563–583.
143. Hudak, K.A.; Parikh, B.A.; Di, R.; Baricevic, M.; Santana, M.; Seskar, M.; Tumer, N.E. Generation of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: Evidence that ribosome depurination is not sufficient for cytotoxicity. Nucleic Acids Res. 2004, 32, 4244–4256.
144. Lappi, D.A.; Wiley, R.G. Immunotoxins and neuropeptide-toxin conjugates experimental applications. Mini Rev. Med. Chem. 2004, 4, 585–595.
145. Jansen, B.; Kersey, J.H.; Jaszcz, W.B.; Gunther, R.; Nguyen, D.P.; Chelstrom, L.M.; Tuel-Ahlgren, L.; Uckun, F.M. Effective immunochemotherapy of human t(4;11) leukemia in mice with severe combined immunodeficiency (SCID) using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin plus cyclophosphamide. Leukemia 1993, 7, 290–297.
146. Uckun, F.M.; Haissig, S.; Ledbetter, J.A.; Fidler, P.; Myers, D.E.; Kuebelbeck, V.; Weisdorf, D.; Gajl-Peczalska, K.; Kersey, J.H.; Ramsay, N.K. Developmental hierarchy during early human B-cell ontogeny after autologous bone marrow transplantation using autografts depleted of CD19+ B-cell precursors by an anti-CD19 pan-B-cell immunotoxin containing pokeweed antiviral protein. Blood 1992, 79, 3369–3379.
147. Uckun, F.M.; Chelstrom, L.M.; Finnegan, D.; Tuel-Ahlgren, L.; Manivel, C.; Irvin, J.D.; Myers, D.E.; Gunther, R. Effective immunochemotherapy of CALLA+C mu+ human pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19) pokeweed antiviral protein immunotoxin plus cyclophosphamide. Blood 1992, 79, 3116–3129.
148. Uckun, F.M.; Chelstrom, L.M.; Irvin, J.D.; Finnegan, D.; Gunther, R.; Young, J.; Kuebelbeck, V.; Myers, D.E.; Houston, L.L. In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia. Blood 1992, 79, 2649–2661.
149. Uckun, F.M.; Manivel, C.; Arthur, D.; Chelstrom, L.M.; Finnegan, D.; Tuel-Ahlgren, L.; Irvin, J.D.; Myers, D.E.; Gunther, R. In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against human pre-B cell acute lymphoblastic leukemia in mice with severe combined immunodeficiency. Blood 1992, 79, 2201–2214.
150. Erice, A.; Balfour, H.H., Jr.; Myers, D.E.; Leske, V.L.; Sannerud, K.J.; Kuebelbeck, V.; Irvin, J.D.; Uckun, F.M. Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein. Antimicrob. Agents Chemother. 1993, 37, 835–838.
151. Zarling, J.M.; Moran, P.A.; Haffar, O.; Sias, J.; Richman, D.D.; Spina, C.A.; Myers, D.E.; Kuebelbeck, V.; Ledbetter, J.A.; Uckun, F.M. Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies. Nature 1990, 347, 92–95.
152. Allen, T.M.; Cullis, P.R. Drug delivery systems: Entering the mainstream. Science 2004, 303, 1818–1822.
153. Baluna, R.; Vitetta, E.S. Vascular leak syndrome: A side effect of immunotherapy. Immunopharmacology 1997, 37, 117–132.
154. Ready, M.P.; Kim, Y.; Robertus, J.D. Site-directed mutagenesis of ricin A-chain and implications for the mechanism of action. Proteins 1991, 10, 270–278.
155. Jasheway, K.; Pruet, J.; Anslyn, E.V.; Robertus, J.D. Structure-based design of ricin inhibitors. Toxins 2011, 3, 1233–1248.
156. Van Regenmortel, M.H.; Fauquet, C.M.; Bishop, D.H.; Carstens, E.B.; Esters, M.K.; Lemon, S.M.; Maniloff, J.; Mayo, M.A.; McGeoch, D.J.; Pringle, C.R. et al. Virus Taxonomy: Seventh Report of the Interanational Committee on Taxonomy of Viruses; Academic Press: San Diego, CA, USA, 2000.
157. Murphy, J.F.; Rychlik, W.; Rhoads, R.E.; Hunt, A.G.; Shaw, J.G. A tyrosine residue in the small nuclear inclusion protein of tobacco vein mottling virus links the VPg to the viral RNA. J. Virol. 1991, 65, 511–513.
158. Goodfellow, I.; Chaudhry, Y.; Gioldasi, I.; Gerondopoulos, A.; Natoni, A.; Labrie, L.; Laliberte, J.F.; Roberts, L. Calicivirus translation initiation requires an interaction between VPg and eIF 4 E. EMBO Rep. 2005, 6, 968–972.
159. Leonard, S.; Plante, D.; Wittmann, S.; Daigneault, N.; Fortin, M.G.; Laliberte, J.F. Complex formation between potyvirus VPg and translation eukaryotic initiation factor 4E correlates with virus infectivity. J. Virol. 2000, 74, 7730–7737.
160. Daughenbaugh, K.F.; Fraser, C.S.; Hershey, J.W.; Hardy, M.E. The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment. EMBO J. 2003, 22, 2852–2859.
161. Urcuqui-Inchima, S.; Haenni, A.L.; Bernardi, F. Potyvirus proteins: A wealth of functions. Virus Res. 2001, 74, 157–175.
162. Wittmann, S.; Chatel, H.; Fortin, M.G.; Laliberte, J.F. Interaction of the viral protein genome linked of turnip mosaic potyvirus with the translational eukaryotic initiation factor (iso) 4E of Arabidopsis thaliana using the yeast two-hybrid system. Virology 1997, 234, 84–92.
163. Khan, M.A.; Miyoshi, H.; Ray, S.; Natsuaki, T.; Suehiro, N.; Goss, D.J. Interaction of genome-linked protein (VPg) of turnip mosaic virus with wheat germ translation initiation factors eIFiso4E and eIFiso4F. J. Biol. Chem. 2006, 281, 28002–28010.
164. Murphy, J.F.; Klein, P.G.; Hunt, A.G.; Shaw, J.G. Replacement of the tyrosine residue that links a potyviral VPg to the viral RNA is lethal. Virology 1996, 220, 535–538.
165. Dunoyer, P.; Thomas, C.; Harrison, S.; Revers, F.; Maule, A. A cysteine-rich plant protein potentiates Potyvirus movement through an interaction with the virus genome-linked protein VPg. J. Virol. 2004, 78, 2301–2309.
166. Nicolas, O.; Dunnington, S.W.; Gotow, L.F.; Pirone, T.P.; Hellmann, G.M. Variations in the VPg protein allow a potyvirus to overcome va gene resistance in tobacco. Virology 1997, 237, 452–459.
167. Rajamaki, M.L.; Valkonen, J.P. The 6K2 protein and the VPg of potato virus A are determinants of systemic infection in Nicandra physaloides. Mol. Plant-Microbe Interact. 1999, 12, 1074–1081.
168. Rajamaki, M.L.; Valkonen, J.P. Viral genome-linked protein (VPg) controls accumulation and phloem-loading of a potyvirus in inoculated potato leaves. Mol. Plant-Microbe Interact. 2002, 15, 138–149.
169. Schaad, M.C.; Carrington, J.C. Suppression of long-distance movement of tobacco etch virus in a nonsusceptible host. J. Virol. 1996, 70, 2556–2561.
170. Schaad, M.C.; Lellis, A.D.; Carrington, J.C. VPg of tobacco etch potyvirus is a host genotype-specific determinant for long-distance movement. J. Virol. 1997, 71, 8624–8631.
171. Rutenber, E.; Katzin, B.J.; Ernst, S.; Collins, E.J.; Mlsna, D.; Ready, M.P.; Robertus, J.D. Crystallographic refinement of ricin to 2.5 A. Proteins 1991, 10, 240–250.
172. Kim, Y.; Mlsna, D.; Monzingo, A.F.; Ready, M.P.; Frankel, A.; Robertus, J.D. Structure of a ricin mutant showing rescue of activity by a noncatalytic residue. Biochemistry 1992, 31, 3294–3296.
173. Khan, M.A.; Miyoshi, H.; Gallie, D.R.; Goss, D.J. Potyvirus genome-linked protein, VPg, directly affects wheat germ in vitro translation: Interactions with translation initiation factors eIF4F and eIFiso4F. J. Biol. Chem. 2008, 283, 1340–1349.
174. Roudet-Tavert, G.; Michon, T.; Walter, J.; Delaunay, T.; Redondo, E.; Le Gall, O. Central domain of a potyvirus VPg is involved in the interaction with the host translation initiation factor eIF4E and the viral protein HcPro. J. Gen. Virol. 2007, 88, 1029–1033.
175. Ghetie, V.; Vitetta, E. Immunotoxins in the therapy of cancer: From bench to clinic. Pharmacol. Ther. 1994, 63, 209–234.
176. Pai, L.H.; Pastan, I. Immunotoxin therapy for cancer. JAMA 1993, 269, 78–81.
177. Frankel, A.E.; Tagge, E.P.; Willingham, M.C. Clinical trials of targeted toxins. Semin. Cancer Biol. 1995, 6, 307–317.
178. Ghetie, M.A.; Vitetta, E.S. Recent developments in immunotoxin therapy. Curr. Opin. Immunol. 1994, 6, 707–714.
179. Grossbard, M.L.; Nadler, L.M. Immunotoxin therapy of lymphoid neoplasms. Semin. Hematol. 1994, 31, 88–97.
180. Anderson, P.M.; Meyers, D.E.; Hasz, D.E.; Covalcuic, K.; Saltzman, D.; Khanna, C.; Uckun, F.M. In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral protein. Cancer Res. 1995, 55, 1321–1327.
181. Waurzyniak, B.; Schneider, E.A.; Tumer, N.; Yanishevski, Y.; Gunther, R.; Chelstrom, L.M.; Wendorf, H.; Myers, D.E.; Irvin, J.D.; Messinger, Y.; et al. In vivo toxicity, pharmacokinetics, and antileukemic activity of TXU (anti-CD7)-pokeweed antiviral protein immunotoxin. Clin. Cancer Res. 1997, 3, 881–890.
182. Allen, T.M.; Martin, F.J. Advantages of liposomal delivery systems for anthracyclines. Semin. Oncol. 2004, 31, 5–15.
183. Medina, O.P.; Zhu, Y.; Kairemo, K. Targeted liposomal drug delivery in cancer. Curr. Pharm. Des. 2004, 10, 2981–2989.
184. Bose, S.; Tuunainen, I.; Parry, M.; Medina, O.P.; Mancini, G.; Kinnunen, P.K. Binding of cationic liposomes to apoptotic cells. Anal. Biochem. 2004, 331, 385–394.