Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Nov 25;19(22):6107–6112. doi: 10.1093/nar/19.22.6107

Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1.

K Yamamoto 1, S Mori 1, T Okamoto 1, K Shimotohno 1, Y Kyogoku 1
PMCID: PMC329097  PMID: 1956769

Abstract

Two different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line. One of the factors bound to a novel dyad symmetrical sequence. This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene. Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay. The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE. However, this factor did not bind to a typical AP-1 site. The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively. Thus, each factor may function as a novel negative regulator of transcription.

Full text

PDF
6107

Images in this article

Selected References

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

  1. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  2. Arya S. K., Guo C., Josephs S. F., Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. doi: 10.1126/science.2990040. [DOI] [PubMed] [Google Scholar]
  3. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  4. Carthew R. W., Chodosh L. A., Sharp P. A. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985 Dec;43(2 Pt 1):439–448. doi: 10.1016/0092-8674(85)90174-6. [DOI] [PubMed] [Google Scholar]
  5. Cooney A. J., Tsai S. Y., O'Malley B. W., Tsai M. J. Chicken ovalbumin upstream promoter transcription factor binds to a negative regulatory region in the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1991 Jun;65(6):2853–2860. doi: 10.1128/jvi.65.6.2853-2860.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cullen B. R., Greene W. C. Regulatory pathways governing HIV-1 replication. Cell. 1989 Aug 11;58(3):423–426. doi: 10.1016/0092-8674(89)90420-0. [DOI] [PubMed] [Google Scholar]
  7. Dasgupta P., Saikumar P., Reddy C. D., Reddy E. P. Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8090–8094. doi: 10.1073/pnas.87.20.8090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dinter H., Chiu R., Imagawa M., Karin M., Jones K. A. In vitro activation of the HIV-1 enhancer in extracts from cells treated with a phorbol ester tumor promoter. EMBO J. 1987 Dec 20;6(13):4067–4071. doi: 10.1002/j.1460-2075.1987.tb02752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  11. Franza B. R., Jr, Rauscher F. J., 3rd, Josephs S. F., Curran T. The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. Science. 1988 Mar 4;239(4844):1150–1153. doi: 10.1126/science.2964084. [DOI] [PubMed] [Google Scholar]
  12. Fukasawa M., Miura T., Hasegawa A., Morikawa S., Tsujimoto H., Miki K., Kitamura T., Hayami M. Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group. Nature. 1988 Jun 2;333(6172):457–461. doi: 10.1038/333457a0. [DOI] [PubMed] [Google Scholar]
  13. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  14. Garcia J. A., Harrich D., Soultanakis E., Wu F., Mitsuyasu R., Gaynor R. B. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. EMBO J. 1989 Mar;8(3):765–778. doi: 10.1002/j.1460-2075.1989.tb03437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garcia J. A., Wu F. K., Mitsuyasu R., Gaynor R. B. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus. EMBO J. 1987 Dec 1;6(12):3761–3770. doi: 10.1002/j.1460-2075.1987.tb02711.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Griffin G. E., Leung K., Folks T. M., Kunkel S., Nabel G. J. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B. Nature. 1989 May 4;339(6219):70–73. doi: 10.1038/339070a0. [DOI] [PubMed] [Google Scholar]
  18. Hauber J., Cullen B. R. Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat. J Virol. 1988 Mar;62(3):673–679. doi: 10.1128/jvi.62.3.673-679.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hong F. D., Huang H. J., To H., Young L. J., Oro A., Bookstein R., Lee E. Y., Lee W. H. Structure of the human retinoblastoma gene. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5502–5506. doi: 10.1073/pnas.86.14.5502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones K. A., Luciw P. A., Duchange N. Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters. Genes Dev. 1988 Sep;2(9):1101–1114. doi: 10.1101/gad.2.9.1101. [DOI] [PubMed] [Google Scholar]
  21. Kaufman J. D., Valandra G., Roderiquez G., Bushar G., Giri C., Norcross M. A. Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element. Mol Cell Biol. 1987 Oct;7(10):3759–3766. doi: 10.1128/mcb.7.10.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kawakami K., Scheidereit C., Roeder R. G. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700–4704. doi: 10.1073/pnas.85.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  24. Lu Y. C., Touzjian N., Stenzel M., Dorfman T., Sodroski J. G., Haseltine W. A. Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1. J Virol. 1990 Oct;64(10):5226–5229. doi: 10.1128/jvi.64.10.5226-5229.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lu Y., Stenzel M., Sodroski J. G., Haseltine W. A. Effects of long terminal repeat mutations on human immunodeficiency virus type 1 replication. J Virol. 1989 Sep;63(9):4115–4119. doi: 10.1128/jvi.63.9.4115-4119.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maekawa T., Itoh F., Okamoto T., Kurimoto M., Imamoto F., Ishii S. Identification and purification of the enhancer-binding factor of human immunodeficiency virus-1. Multiple proteins and binding to other enhancers. J Biol Chem. 1989 Feb 15;264(5):2826–2831. [PubMed] [Google Scholar]
  27. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  28. McGee T. L., Yandell D. W., Dryja T. P. Structure and partial genomic sequence of the human retinoblastoma susceptibility gene. Gene. 1989 Aug 1;80(1):119–128. doi: 10.1016/0378-1119(89)90256-4. [DOI] [PubMed] [Google Scholar]
  29. Mori S., Takada R., Shimotohno K., Okamoto T. Repressive effect of the nef cDNA of human immunodeficiency virus type 1 on the promoter activity of the viral long terminal repeat. Jpn J Cancer Res. 1990 Nov;81(11):1124–1131. doi: 10.1111/j.1349-7006.1990.tb02523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  31. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  32. Okamoto T., Wong-Staal F. Demonstration of virus-specific transcriptional activator(s) in cells infected with HTLV-III by an in vitro cell-free system. Cell. 1986 Oct 10;47(1):29–35. doi: 10.1016/0092-8674(86)90363-6. [DOI] [PubMed] [Google Scholar]
  33. Orchard K., Perkins N., Chapman C., Harris J., Emery V., Goodwin G., Latchman D., Collins M. A novel T-cell protein which recognizes a palindromic sequence in the negative regulatory element of the human immunodeficiency virus long terminal repeat. J Virol. 1990 Jul;64(7):3234–3239. doi: 10.1128/jvi.64.7.3234-3239.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Peterlin B. M., Luciw P. A., Barr P. J., Walker M. D. Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734–9738. doi: 10.1073/pnas.83.24.9734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature. 1986 Feb 13;319(6054):555–559. doi: 10.1038/319555a0. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Shaw J. P., Utz P. J., Durand D. B., Toole J. J., Emmel E. A., Crabtree G. R. Identification of a putative regulator of early T cell activation genes. Science. 1988 Jul 8;241(4862):202–205. doi: 10.1126/science.3260404. [DOI] [PubMed] [Google Scholar]
  38. Shimotohno K., Takano M., Teruuchi T., Miwa M. Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112–8116. doi: 10.1073/pnas.83.21.8112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science. 1987 Dec 11;238(4833):1575–1578. doi: 10.1126/science.2825351. [DOI] [PubMed] [Google Scholar]
  40. Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. doi: 10.1126/science.2990041. [DOI] [PubMed] [Google Scholar]
  41. Tong-Starksen S. E., Luciw P. A., Peterlin B. M. Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845–6849. doi: 10.1073/pnas.84.19.6845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Varmus H. Regulation of HIV and HTLV gene expression. Genes Dev. 1988 Sep;2(9):1055–1062. doi: 10.1101/gad.2.9.1055. [DOI] [PubMed] [Google Scholar]
  43. Wu F. K., Garcia J. A., Harrich D., Gaynor R. B. Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1. EMBO J. 1988 Jul;7(7):2117–2130. doi: 10.1002/j.1460-2075.1988.tb03051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES