"Translocatory proteins" and "protein transduction domains": A critical analysis of their biological effects and the underlying mechanisms

Molecular Therapy

Volumn 8, Issue 1, 2003, Pages 13-20

  Leifert, Jens A ^a,b   Whitton, J Lindsay ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALUMINUM HYDROXIDE; BETA GALACTOSIDASE; BETA GLUCURONIDASE; CARRIER PROTEIN; CD8 ANTIGEN; DNA VACCINE; GAMMA INTERFERON; GANCICLOVIR; HOMEODOMAIN PROTEIN; HYBRID PROTEIN; IMMUNOGLOBULIN G; INTERLEUKIN 4; LACTOFERRIN; LIPOSOME; OVALBUMIN; POLYPEPTIDE; PROTEIN P53; SAPONIN; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR; VIRUS PROTEIN;

CELL SECRETION; CELL TRANSPORT; CYTOTOXIC T LYMPHOCYTE; DRUG RESEARCH; ENDOCYTOSIS; GENE THERAPY; GENE TRANSLOCATION; GENETIC TRANSFECTION; HERPES SIMPLEX VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; MEDICAL LITERATURE; MOLECULAR BIOLOGY; MOLECULAR MECHANICS; NONHUMAN; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN SYNTHESIS; REVIEW; TEMPERATURE MEASUREMENT; VETERINARY MEDICINE; VIRAL GENE DELIVERY SYSTEM;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; SIMPLEXVIRUS;

EID: 0041698459     PISSN: 15250016     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1525-0016(03)00151-5     Document Type: Review

References (98)

1. Prochiantz, A. (2000). Messenger proteins: Homeoproteins, TAT and others. Curr. Opin. Cell Biol. 12: 400-406.
2. Lindgren, M., Hallbrink, M., Prochiantz, A., and Langel, U. (2000). Cell-penetrating peptides. Trends Pharmacol. Sci. 21: 99-103.
3. Ford, K. G., Souberbielle, B. E., Darling, D., and Farzaneh, F. (2001). Protein transduction: An alternative to genetic intervention? Gene Ther. 8: 1-4.
4. Elliott, G., and O'Hare, P. (1997). Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 88: 223-233.
5. Echols, N., et al. (2002). Comprehensive analysis of amino acid and nucleotide composition in eukaryotic genomes, comparing genes and pseudogenes. Nucleic Acids Res. 30: 2515-2523.
6. + T cell differentiation: Initial antigen encounter triggers a developmental program in naïve cells. Nat. Immunol. 2: 415-422.
7. van Stipdonk, M. J., Lemmens,, E. E., and Schoenberger, S. P. (2001). Naive CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat. Immunol. 2: 423-429.
8. Moore, M. W., Carbone, F. R., and Bevan, M. J. (1988). Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell 54: 777-785.
9. Rock, K. L. (1996). A new foreign policy: MHC class I molecules monitor the outside world. Immunol. Today 17: 131-137.
10. Watts, C. (1997). Capture and processing of exagenous antigens for presentation on MHC molecules. Annu. Rev. Immunol. 15: 821-850.
11. Sigal, L. J., Crotty, S., Andino, R., and Rock, K. L. (1999). Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature 398: 77-80.
12. Carbone, F. R., Kurts, C., Bennett, S. R., Miller, J. F., and Heath, W. R. (1998). Cross-presentation: A general mechanism for CTL immunity and tolerance. Immunol. Today 19: 368-373.
13. Elliott, G. D., and Meredith, D. M. (1992). The herpes simplex virus type 1 tegument protein VP22 is encoded by gene UL49. J. Gen. Virol. 73: 723-726.
14. Elliott, G., O'Reilly, D., and O'Hare, P. (1996). Phosphorylation of the herpes simplex virus type 1 tegument protein VP22. Virology 226: 140-145.
15. Blaho, J. A., Mitchell, C., and Roizman, B. (1994). An amino acid sequence shared by the herpes simplex virus 1 alpha regulatory proteins 0, 4, 22, and 27 predicts the nucleotidylation of the UL21, UL31, UL47, and UL49 gene products. J. Biol. Chem. 269: 17401-17410.
16. Phelan, A., Elliott, G., and O'Hare, P. (1998). Intercellular delivery of functional p53 by the herpesvirus protein VP22. Nat. Biotechnol. 16: 440-443.
17. Dilber, M. S., et al. (1999). Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22. Gene Ther. 6: 12-21.
18. Cheng, W. F., et al. (2002). Cancer immunotherapy using Sindbis virus replicon particles encoding a VP22-antigen fusion. Hum. Gene Ther. 13: 553-568.
19. Cheng, W. F., et al. (2001). Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of herpes simplex virus type 1 VP22 protein to antigen. J. Virol. 75: 2368-2376.
20. Hung, C. F., et al. (2001). Improving vaccine potency through intercellular spreading and enhanced MHC class I presentation of antigen. J. Immunol. 166: 5733-5740.
21. Michel, N., et al. (2002). Enhanced immunogenicity of HPV 16 E7 fusion proteins in DNA vaccination. Virology 294: 47-59.
22. Hung, C. F., et al. (2002). Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen. J. Virol. 76: 2676-2682.
23. Oliveira, S. C., Harms, J. S., Afonso, R. R., and Splitter, G. A. (2001). A genetic immunization adjuvant system based on BVP22-antigen fusion. Hum. Gene Ther. 12: 1353-1359.
24. Zender, L., Kuhnel, F., Kock, R., Manns, M., and Kubicka, S. (2002). VP22-mediated intercellular transport of p53 in hepatoma cells in vitro and in vivo. Cancer Gene Ther. 9: 489-496.
25. Zender, L., et al. (2002). Gene therapy by intrahepatic and intratumoral trafficking of p53-VP22 induces regression of liver tumors. Gastroenterology 123: 608-618.
26. McGinnis, W., Levine, M. S., Hafen, E., Kuroiwa, A., and Gehring, W. J. (1984). A conserved DNA sequence in homeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 308: 428-433.
27. Scott, M. P., and Weiner, A. J. (1984). Structural relationships among genes that control development: Sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Proc. Natl. Acad. Sci. USA 81: 4115-4119.
28. Gehring, W. J., Affolter, M., and Burglin, T. (1994). Homeodomain proteins. Annu. Rev. Biochem. 63: 487-526.
29. Dorn, A., Affolter, M., Gehring, W. J., and Leupin, W. (1994). Homeodomain proteins in development and therapy. Pharmacol. Ther. 61: 155-184.
30. Gehring, W. J. (1993). Exploring the homeobox. Gene 135: 215-221.
31. Joliot, A. H., Triller, A., Volovitch, M., Pernelle, C., and Prochiantz, A. (1991). alpha-2,8-Polysialic acid is the neuronal surface receptor of antennapedia homeobox peptide. New Biol. 3: 1121-1134.
32. Schutze-Redelmeier, M. P., et al. (1996). Introduction of exogenous antigens into the MHC class I processing and presentation pathway by Drosophila antennapedia homeodomain primes cytotoxic T cells in vivo. J. Immunol. 157: 650-655.
33. + T lymphocyte-mediated antiviral immunity in mice as a result of injection of recombinant viral proteins. J. Immunol. 153: 2554-2561.
34. Bachmann, M. F., et al. (1994). Induction of protective cytotoxic T cells with viral proteins. Eur. J. Immunol. 24: 2228-2236.
35. Chikh, G., Bally, M., and Schutze-Redelmeier, M. P. (2001). Characterization of hybrid CTL epitope delivery systems consisting of the Antennapedia homeodomain peptide vector formulated in liposomes. J. Immunol. Methods 254: 119-135.
36. T cells. J. Immunol. 167: 6462-6470.
37. Derossi, D., Chassaing, G., and Prochiantz, A. (1998). Trojan peptides: The penetratin system for intracellular delivery. Trends Cell Biol. 8: 84-87.
38. Fischer, P. M., et al. (2000). Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector penetratin. J. Pept. Res. 55: 163-172.
39. Theodore, L., et al. (1995). Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse. J. Neurosci. 15: 7158-7167.
40. Derossi, D., et al. (1996). Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J. Biol. Chem. 271: 18188-18193.
41. Pietersz, G. A., Li, W., and Apostolopoulos, V. (2001). A 16-mer peptide (RQIKIWFQN-RRMKWKK) from antennapedia preferentially targets the Class I pathway. Vaccine 19: 1397-1405.
42. Chatelin, L., Volovitch, M., Joliot, A. H., Perez, F., and Prochiantz, A. (1996). Transcription factor hoxa-5 is taken up by cells in culture and conveyed to their nuclei. Mech. Dev. 55: 111-117.
43. Pooga, M., et al. (1998). Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat. Biotechnol. 16: 857-861.
44. Hosotani, R., et al, (2002). Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice. Clin. Cancer Res. 8: 1271-1276.
45. Benelli, R., et al. (2000). Human immunodeficiency virus transactivator protein (Tat) stimulates chemotaxis, calcium mobilization, and activation of human polymorphonuclear leukocytes: Implications for Tat-mediated pathogenesis. J. Infect. Dis. 182: 1643-165.
46. Albini, A., et al. (1998). Identification of a novel domain of HIV tat involved in monocyte chemotaxis. J. Biol. Chem. 273: 15895-15900.
47. Albini, A., et al. (1998). HIV-1 Tat protein mimicry of chemokines. Proc. Natl. Acad. Sci. USA 95: 13153-13158.
48. Benelli, R., et al. (1998). Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic peptides. AIDS 12: 261-268.
49. Arese, M., Ferrandi, C., Primo, L., Camussi, G., and Bussolino, F. (2001). HIV-1 Tat protein stimulates in vivo vascular permeability and lymphomononuclear cell recruitment. J. Immunol. 166: 1380-1388.
50. Ott, M., et al. (1997). Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway. Science 275: 1481-1485.
51. Ott, M., Lovett, J. L., Mueller, L., and Verdin, E. (1998). Superinduction of IL-8 in T cells by HIV-1 Tat protein is mediated through NF-kappaB factors. J. Immunol. 160: 2872-2880.
52. Brake, D. A., et al. (1990). Characterization of murine monoclonal antibodies to the tat protein from human immunodeficiency virus type 1. J. Virol. 64: 962-965.
53. Kim, D. T., et al. (1997). Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide. J. Immunol. 159: 1666-1668.
54. Shibagaki, N., and Udey, M. C. (2002). Dendritic cells transduced with protein antigens induce cytotoxic lymphocytes and elicit antitumor immunity. J. Immunol. 168: 2393-2401.
55. + T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells. J. Clin. Invest. 109: 1463-1470.
56. Leifert, J. A., Lindencrona, J. A., Charo, J., and Whitton, J. L. (2001). Enhancing T cell activation and antiviral protection by introducing the HIV-1 protein transduction domain into a DNA vaccine. Hum. Gene Ther. 12:1881-1892.
57. Leifert, J. A., Harkins, S., and Whitton, J. L. (2002). Full-length proteins attached to the HIV tat protein transduction domain are neither transduced between cells, nor exhibit enhanced immunogenicity. Gene Ther. 9: 1422-1428.
58. Wadia, J. S., and Dowdy, S. F. (2002). Protein transduction technology. Curr. Opin. Biotechnol. 13: 52-56.
59. Fawell, S., et al. (1994). Tat-mediated delivery of heterologous proteins into cells. Proc. Natl. Acad. Sci. USA 91: 664-668.
60. Schwarze, S. R., Ho, A., Vocero-Akbani, A., and Dowdy, S. F. (1999). In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science 285: 1569-1572.
61. Nagahara, H., et al. (1998). Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nat. Med. 4: 1449-1452.
62. Vocero-Akbani, A., Lissy, N. A., and Dowdy, S. F. (2000). Transduction of full-length Tat fusion proteins directly into mammalian cells: Analysis of T cell receptor activation-induced cell death. Methods Enzymol. 322: 508-521.
63. Becker-Hapak, M., McAllister, S. S., and Dowdy, S. F. (2001). TAT-mediated protein transduction into mammalian cells. Methods 24: 247-256.
64. Cao, G., et al. (2002). In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J. Neurosci. 22: 5423-5431.
65. Xia, H., Mao, Q., and Davidson, B. L. (2001). The HIV Tat protein transduction domain improves the biodistribution of beta-glucuronidase expressed from recombinant viral vectors. Nat. Biotechnol. 19: 640-644.
66. Joliot, A., et al. (1998). Identification of a signal sequence necessary for the unconventional secretion of Engrailed homeoprotein. Curr. Biol. 8: 856-863.
67. Falnes, P. O., Wesche, J., and Olsnes, S. (2001). Ability of the Tat basic domain and VP22 to mediate cell binding, but not membrane translocation of the diphtheria toxin A-fragment. Biochemistry 40: 4349-4358.
68. Mai, J. C., Shen, H., Watkins, S. C., Cheng, T., and Robbins, P. D. (2002). Efficiency of protein transduction is cell type-dependent and is enhanced by dextran sulfate. J. Biol. Chem. 277: 30208-30218.
69. Fang, B., Xu, B., Koch, P., and Roth, J. A. (1998). Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells. Gene Ther. 5: 1420-1424.
70. Elliott, G., and O'Hare, P. (1999). Intercellular trafficking of VP22-GFP fusion proteins. Gene Ther. 6: 149-151.
71. Brewis, N., et al. (2000). Evaluation of VP22 spread in tissue culture. J. Virol. 74: 1051-1056.
72. Aints, A., Dilber, M. S., and Smith, C. I. (1999). Intercellular spread of GFP-VP22. J. Gene Med. 1: 275-279.
73. Lundberg, M., and Johansson, M. (2001). Is VP22 nuclear homing an artifact? Nat. Biotechnol. 19: 713-714.
74. Lundberg, M., and Johansson, M. (2002). Positively charged DNA-binding proteins cause apparent cell membrane translocation. Biochem. Biophys. Res. Commun. 291: 367-371.
75. Richard, J. P., et al. (2003). Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. J. Biol. Chem. 278: 585-590.
76. Falnes, P. O., Ariansen, S., Sandvig, K., and Olsnes, S, (2000). Requirement for prolonged action in the cytosol for optimal protein synthesis inhibition by diphtheria toxin. J. Biol. Chem. 275: 4363-4368.
77. Peitz, M., Pfannkuche, K., Rajewsky, K., and Edenhofer, F. (2002). Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: A tool for efficient genetic engineering of mammalian genomes. Proc. Natl. Acad. Sci. USA 99: 4489-4494.
78. Bennett, R. P., Dalby, B., and Guy, P. M. (2002). Protein delivery using VP22. Nat. Biotechnol. 20: 20.
79. Wiedlocha, A., Falnes, P. O., Madshus, I. H., Sandvig, K., and Olsnes, S. (1994). Dual mode of signal transduction by externally added acidic fibroblast growth factor. Cell 76: 1039-1051.
80. Arora, N., Williamson, L. C., Leppla, S. H., and Halpern, J. L. (1994). Cytotoxic effects of a chimeric protein consisting of tetanus toxin light chain and anthrax toxin lethal factor in non-neuronal cells. J. Biol. Chem. 269: 26165-26171.
81. Arora, N., and Leppla, S. H. (1994). Fusions of anthrax toxin lethal factor with shiga toxin and diphtheria toxin enzymatic domains are toxic to mammalian cells. Infect. Immun. 62: 4955-4961.
82. Fuki, I. V., Meyer, M. E., and Williams, K. J. (2000). Transmembrane and cytoplasmic domains of syndecan mediate a multi-step endocytic pathway involving detergent-insoluble membrane rafts. Biochem. J. 351: 607-612.
83. Rothbard, J. B., et al. (2000). Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat. Med, 6: 1253-1257.
84. Ho, A., Schwarze, S. R., Mermelstein, S. J., Waksman, G., and Dowdy, S. F. (2001). Synthetic protein transduction domains: Enhanced transduction potential in vitro and in vivo. Cancer Res. 61: 474-477.
85. Futaki, S., et al. (2001). Stearylated arginine-rich peptides: A new class of transfection systems. Bioconjugate Chem. 12: 1005-1011.
86. Rothbard, J. B., et al. (2002). Arginine-rich molecular transporters for drug delivery: Role of backbone spacing in cellular uptake. J. Med. Chem. 45: 3612-3618.
87. Shen, W. C., and Ryser, H. J. (1978). Conjugation of poly-L-lysine to albumin and horseradish peroxidase: A novel method of enhancing the cellular uptake of proteins. Proc. Natl. Acad. Sci. USA 75: 1872-1876.
88. Ryser, H. J., Drummond, I., and Shen, W. C. (1982). The cellular uptake of horseradish peroxidase and its poly(lysine) conjugate by cultured fibroblasts is qualitatively similar despite a 900-fold difference in rate. J. Cell. Physiol. 113: 167-178.
89. Lührs, P., et al. (2002). Induction of specific immune responses by polycation-based vaccines. J. Immunol. 169: 5217-5226.
90. Albini, A., et al. (1996). HIV-tat protein is a heparin-binding angiogenic growth factor. Oncogene 12: 289-297.
91. Vives, E., Brodin, P., and Lebleu, B. (1997). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272: 16010-16017.
92. Kueltzo, L. A., Normand, N., O'Hare, P., and Middaugh, C. R. (2000). Conformational lability of herpesvirus protein VP22. J. Biol. Chem. 275: 33213-33221.
93. Colin, S., et al. (1999). In vivo involvement of heparan sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor. Mol. Pharmacol. 55: 74-82.
94. Pellegrini, L. (2001). Role of heparan sulfate in fibroblast growth factor signalling: A structural view. Curr. Opin. Struct. Biol. 11: 629-634.
95. Guerrini, M., et al. (2002). Minimal heparin/heparan sulfate sequences for binding to fibroblast growth factor-1. Biochem. Biophys. Res. Commun. 292: 222-230.
96. Amalric, F., et al. (1994). Fibroblast growth factor-2 (FGF-2) in the nucleus: Translocation process and targets. Biochem. Pharmacol. 47: 111-115.
97. Damiens, E., et al. (1998). Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line. Eur. J. Cell Biol. 77: 344-351.
98. Penco, S., et al. (2001). Identification of an import signal for, and the nuclear localization of, human lactoferrin. Biotechnol. Appl. Biochem. 34: 151-159.