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. 1992 Oct 15;89(20):9617–9621. doi: 10.1073/pnas.89.20.9617

Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells.

J P Taylor 1, C Cupp 1, A Diaz 1, M Chowdhury 1, K Khalili 1, S A Jimenez 1, S Amini 1
PMCID: PMC50183  PMID: 1409674

Abstract

The Tat protein of human immunodeficiency virus type 1 has been increasingly implicated in directly contributing to the disease AIDS by altering the expression of strategic cellular genes. In this study we demonstrate that the presence of the human immunodeficiency virus type 1 regulatory protein Tat is associated with a significant induction in the expression of certain protein components of the extracellular matrix in glial-derived cells. Northern blot analysis reveals that in cells expressing Tat there is a marked elevation in the steady-state RNA levels for fibronectin and types I and III collagen. Metabolic labeling of the Tat-producing cells demonstrates that this induction is also reflected at the level of protein synthesis. Transient transfection experiments indicate that the presence of Tat results in increased transcription of fibronectin and alpha I type I collagen promoters. Possible mechanisms for this phenomenon and their significance with regard to AIDS are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berkhout B., Gatignol A., Rabson A. B., Jeang K. T. TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell. 1990 Aug 24;62(4):757–767. doi: 10.1016/0092-8674(90)90120-4. [DOI] [PubMed] [Google Scholar]
  2. Bornstein P., McKay J., Morishima J. K., Devarayalu S., Gelinas R. E. Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8869–8873. doi: 10.1073/pnas.84.24.8869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bruckner P., Prockop D. J. Proteolytic enzymes as probes for the triple-helical conformation of procollagen. Anal Biochem. 1981 Jan 15;110(2):360–368. doi: 10.1016/0003-2697(81)90204-9. [DOI] [PubMed] [Google Scholar]
  4. Chu M. L., Myers J. C., Bernard M. P., Ding J. F., Ramirez F. Cloning and characterization of five overlapping cDNAs specific for the human pro alpha 1(I) collagen chain. Nucleic Acids Res. 1982 Oct 11;10(19):5925–5934. doi: 10.1093/nar/10.19.5925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cullen B. R. Regulation of HIV-1 gene expression. FASEB J. 1991 Jul;5(10):2361–2368. doi: 10.1096/fasebj.5.10.1712325. [DOI] [PubMed] [Google Scholar]
  6. Dean D. C., Bowlus C. L., Bourgeois S. Cloning and analysis of the promotor region of the human fibronectin gene. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1876–1880. doi: 10.1073/pnas.84.7.1876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dean D. C., Newby R. F., Bourgeois S. Regulation of fibronectin biosynthesis by dexamethasone, transforming growth factor beta, and cAMP in human cell lines. J Cell Biol. 1988 Jun;106(6):2159–2170. doi: 10.1083/jcb.106.6.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ensoli B., Barillari G., Salahuddin S. Z., Gallo R. C., Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature. 1990 May 3;345(6270):84–86. doi: 10.1038/345084a0. [DOI] [PubMed] [Google Scholar]
  9. Frankel A. D., Pabo C. O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988 Dec 23;55(6):1189–1193. doi: 10.1016/0092-8674(88)90263-2. [DOI] [PubMed] [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  12. Harrich D., Garcia J., Mitsuyasu R., Gaynor R. TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes. EMBO J. 1990 Dec;9(13):4417–4423. doi: 10.1002/j.1460-2075.1990.tb07892.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haseltine W. A. Molecular biology of the human immunodeficiency virus type 1. FASEB J. 1991 Jul;5(10):2349–2360. doi: 10.1096/fasebj.5.10.1829694. [DOI] [PubMed] [Google Scholar]
  14. Helland D. E., Welles J. L., Caputo A., Haseltine W. A. Transcellular transactivation by the human immunodeficiency virus type 1 tat protein. J Virol. 1991 Aug;65(8):4547–4549. doi: 10.1128/jvi.65.8.4547-4549.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ignotz R. A., Endo T., Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987 May 15;262(14):6443–6446. [PubMed] [Google Scholar]
  16. Kamine J., Subramanian T., Chinnadurai G. Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8510–8514. doi: 10.1073/pnas.88.19.8510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  18. Kopp J. B., Klotman M. E., Adler S. H., Bruggeman L. A., Dickie P., Marinos N. J., Eckhaus M., Bryant J. L., Notkins A. L., Klotman P. E. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1577–1581. doi: 10.1073/pnas.89.5.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Isolation and characterization of cDNA clones for human and bovine fibronectins. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3218–3222. doi: 10.1073/pnas.80.11.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Merrill J. E., Chen I. S. HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J. 1991 Jul;5(10):2391–2397. doi: 10.1096/fasebj.5.10.2065887. [DOI] [PubMed] [Google Scholar]
  21. Navia B. A., Price R. W. The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. Arch Neurol. 1987 Jan;44(1):65–69. doi: 10.1001/archneur.1987.00520130051017. [DOI] [PubMed] [Google Scholar]
  22. Price R. W., Brew B., Sidtis J., Rosenblum M., Scheck A. C., Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. doi: 10.1126/science.3277272. [DOI] [PubMed] [Google Scholar]
  23. Pumarola-Sune T., Navia B. A., Cordon-Cardo C., Cho E. S., Price R. W. HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol. 1987 May;21(5):490–496. doi: 10.1002/ana.410210513. [DOI] [PubMed] [Google Scholar]
  24. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  25. Rosenberg Z. F., Fauci A. S. Immunopathogenesis of HIV infection. FASEB J. 1991 Jul;5(10):2382–2390. doi: 10.1096/fasebj.5.10.1676689. [DOI] [PubMed] [Google Scholar]
  26. Sastry K. J., Reddy H. R., Pandita R., Totpal K., Aggarwal B. B. HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. J Biol Chem. 1990 Nov 25;265(33):20091–20093. [PubMed] [Google Scholar]
  27. Taylor J. P., Pomerantz R., Bagasra O., Chowdhury M., Rappaport J., Khalili K., Amini S. TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J. 1992 Sep;11(9):3395–3403. doi: 10.1002/j.1460-2075.1992.tb05418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Viscidi R. P., Mayur K., Lederman H. M., Frankel A. D. Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science. 1989 Dec 22;246(4937):1606–1608. doi: 10.1126/science.2556795. [DOI] [PubMed] [Google Scholar]
  29. Vogel J., Hinrichs S. H., Reynolds R. K., Luciw P. A., Jay G. The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature. 1988 Oct 13;335(6191):606–611. doi: 10.1038/335606a0. [DOI] [PubMed] [Google Scholar]
  30. Weeks B. S., Klotman M. E., Dhawan S., Kibbey M., Rappaport J., Kleinman H. K., Yamada K. M., Klotman P. E. HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression. J Cell Biol. 1991 Aug;114(4):847–853. doi: 10.1083/jcb.114.4.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proc Natl Acad Sci U S A. 1990 May;87(10):3997–4001. doi: 10.1073/pnas.87.10.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wiley C. A., Nelson J. A. Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am J Pathol. 1988 Oct;133(1):73–81. [PMC free article] [PubMed] [Google Scholar]

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