Characteristics of HIV-Tat Protein Transduction Domain

  • Yoon Jong-Sub (Department of Microbiology, The Catholic University of Korea) ;
  • Jung Yong-Tae (Department of Microbiology, College of Advanced Science, Dankook University) ;
  • Hong Seong-Karp (Catholic Hemopoietic Stem Cell Transplantation Center, The Catholic University of Korea) ;
  • Kim Sun-Hwa (Department of Microbiology, The Catholic University of Korean) ;
  • Shin Min-Chul (Department of Microbiology, The Catholic University of Korean) ;
  • Lee Dong-Gun (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Shin Wan-Shik (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Min Woo-Sung (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Paik Soon-Young (Department of Microbiology, The Catholic University of Korea)
  • Published : 2004.12.01

Abstract

The human immunodeficiency virus type 1 (HIV-I) Tat protein transduction domain (PTD), which con­tains rich arginine and lysine residues, is responsible for the highly efficient transduction of protein through the plasma membrane. In addition, it can be secreted from infected cells and has the ability to enter neighboring cells. When the PTD of Tat is fused to proteins and exogenously added to cells, the fusion protein can cross plasma membranes. Recent reports indicate that the endogenously expressed Tat fusion protein can demonstrate biodistribution of several proteins. However, intercellular transport and protein transduction have not been observed in some studies. Therefore, this study exam­ined the intercellular transport and protein transduction of the Tat protein. The results showed no evi­dence of intercellular transport (biodistribution) in a cell culture. Instead, the Tat fusion peptides were found to have a significant effect on the transduction and intercellular localization properties. This sug­gests that the HIV-1 PTD passes through the plasma membrane in one direction.

Keywords

References

  1. Bao, J.J., W.W. Zhang, and M.T. Kuo. 1996. Adenoviral delivery of recombinant DNA into transgenic mice bearing hepatocellular carcinomas. Hum Gene Ther. 7, 355-365
  2. Bradford, M. A. 1976. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254
  3. Derossi, D., A.H. Joliot, G. Chassaing, and A. Prochiantz. 1994. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem. 269, 10444-10450
  4. Elliger, S., C.A. Elliger, C. Lang, and G.L. Watson. 2002. Enhanced secretion and uptake of beta-glucuronidase improves adenoassociated viral-mediated gene therapy of mucopolysaccharidosis type VII mice. Mol Ther. 5, 617-626
  5. Elliott, G. and P. O'Hare. 1997. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell. 88, 223-233 https://doi.org/10.1016/S0092-8674(00)81843-7
  6. Frankel, A.D. and C.O. Pabo. 1988. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 55, 1189-1193
  7. Futaki, S., T. Suzuki, W. Ohashi, T. Yagami, S. Tanaka, K. Ueda, and Y. Sugiura. 2001. Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J. Biol. Chem. 276, 5836-5840 https://doi.org/10.1074/jbc.M007540200
  8. Gao, G.P., Y. Yang, and J.M. Wilson. 1996. Biology of adenovirus vectors with E1 and E4 deletions for liver-directed gene therapy. J. Virol. 70, 8934-8943
  9. Green, M. and P.M. Loewenstein. 1988. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 55, 1179-1188
  10. Han, K., M.J. Jeon, K.A. Kim, J. Park, and S.Y. Choi. 2000. Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and engrailed proteins. Mol. Cells 10, 728-732
  11. Ho, A., S.R. Schwarze, S.J. Mermelstein, G. Waksman, and S.F. Dowdy. 2001. Synthetic protein transduction domains: enhanced transduction potential in vitro and in vivo. Cancer. Res. 61, 474-477
  12. Joliot, A., C. Pernelle, H. Deagostini-Bazin, and A. Prochiantz. 1991. Antennapedia homeobox peptide regulates neural morphogenesis. Proc. Natl. Acad. Sci. USA. 88, 1864-1868
  13. Leifert, J.A., S. Harkins, and J.L. Whitton. 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
  14. Lieber, A., C.Y. He, L. Meuse, D. Schowalter, I. Kirillova, B. Winther, and M.A. Kay. 1997. The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J. Virol. 71, 8798-8807
  15. Moon, M.S., G.C. Lee, and C.H. Lee. 2002. Induction of Apopotosis in Human Monocytes by Human Cytomegalovirus is Related with Calcium Increase. J. Microbiol. 40, 224-229
  16. Nagahara, H., A.M. Vocero-Akbani, E.L. Snyder, A. Ho, D.G. Latham, N.A. Lissy, M. Becker-Hapak, S.A. Ezhevsky, and S.F. Dowdy. 1998. Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nature Medicine 4, 1449-1452
  17. O'Reilly, D.R., L.K. Miller, and V.A. Luckow. 1992. Baculovirus Expression Vectors: A Laboratory Manual, Oxford Univ Press, New York, USA
  18. Park, J., J. Ryu, K.A. Kim, H.J. Lee, J.H. Bahn, K. Han, E.Y. Choi, K.S. Lee, H.Y. Kwon, and S.Y. Choi. 2002. Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells. J. Gen. Virol. 83, 1173-1181
  19. Park, S.W., H.K. Lee, T.G. Kim, S.K. Yoon, and S.Y. Paik. 2001. Hepatocyte-specific gene expression by baculovirus pseudotyped with vesicular stomatitis virus envelope glycoprotein. Biochem. Biophys. Res. Commun. 289, 444-450
  20. Ryu, J.Y., K.Y. Han, J.S. Park, and S.Y. Choi. 2003. Enhanced uptake of a heterologous protein with an HIV-1 Tat protein transduction domains (PTD) at both termini. Mol. Cells. 16, 385-391
  21. Schwarze, S.R. and S.F. Dowdy. 2000. In vivo protein transduction: Intracellular delivery of biologically active proteins, compounds and DNA. Trends. Pharmacol. Sci. 21, 45-48
  22. Schwarze, S.R., A. Ho, A. Vocero-Akbani, and S.F. Dowdy. 1999. In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569-1572
  23. Silhol, M., M. Tyagi, M. Giacca, B. Lebleu, and E. Vives. 2002. Different mechanisms for cellular internalization of the HIV-1 Tat-derived cell penetrating peptide and recombinant proteins fused to Tat. Eur. J. Biochem. 269, 494-50
  24. Schwarze, S. R. and S. F. Dowdy. 2000. In vivo protein transduction: intracellular delivery of biologically active protein, compounds and DNA. Trends, Pharm, Science. 21, 45-48
  25. Vives, E., P. Brodin, and B. Lebleu. 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 https://doi.org/10.1074/jbc.272.25.16010
  26. Wender, P.A., D.J. Mitchell, K. Pattabiraman, E.T. Pelkey, L. Steinman, and J.B. Rothbard. 2000. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters. Proc. Natl. Acad. Sci. USA. 97, 13003-13008
  27. Xia, H., Q. Mao, and B.L. Davidson. 2001. The HIV Tat protein transduction domain improves the biodistribution of beta-glucuronidase expressed from recombinant viral vectors. Nat. Biotechnol. 19, 640-644