• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Dec 1996; 70(12): 8508–8517.
PMCID: PMC190942

Differential transactivation of the intercellular adhesion molecule 1 gene promoter by Tax1 and Tax2 of human T-cell leukemia viruses.

Abstract

Previously, we showed that surface expression of intercellular adhesion molecule 1 (ICAM-1) was strongly upregulated in T cells carrying proviral human T-cell leukemia virus type 1 (HTLV-1) and that the viral transactivator protein Tax1 was capable of inducing the ICAM-1 gene. To determine the responsive elements in the human ICAM-1 gene promoter, a reporter construct in which the 5'-flanking 4.4-kb region of the ICAM-1 gene was linked to the promoterless chloramphenicol acetyltransferase (CAT) gene was cotransfected with expression vectors for Tax1 and Tax2, both of which were separately confirmed to be potent transactivators of the HTLV-1 long terminal repeat (LTR). Tax1 strongly activated the ICAM-1 promoter in all the cell lines tested: three T-cell lines (Jurkat, MOLT-4, and CEM), one monocytoid cell line (U937), and HeLa. Unexpectedly, Tax2 activated the ICAM-1 promoter only in HeLa. By deletion and mutation analyses of the 1.3-kb 5'-flanking region, we found that Tax1 transactivated the ICAM-1 promoter mainly via a cyclic AMP-responsive element (CRE)-like site at -630 to -624 in the Jurkat T-cell line and via an NF-kappaB site at -185 to -177 and an SP-1 site at -59 to -54 in HeLa. On the other hand, Tax2 was totally inactive on the ICAM-1 promoter in Jurkat but transactivated the promoter via the NF-kappaB site at -185 to -177 in HeLa. Gel mobility shift assays demonstrated proteins specifically binding to the CRE-like site at -630 to -624 in Tax1-expressing T-cell lines. Stable expression of Tax1 but not Tax2 in Jurkat subclones enhanced the surface expression of ICAM-1. The differential ability of Tax1 and Tax2 in transactivation of the ICAM-1 gene may be related to the differential pathogenicity of HTLV-1 and HTLV-2.

Full Text

The Full Text of this article is available as a PDF (415K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Armstrong AP, Franklin AA, Uittenbogaard MN, Giebler HA, Nyborg JK. Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7303–7307. [PMC free article] [PubMed]
  • Baba M, Imai T, Yoshida T, Yoshie O. Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax. Int J Cancer. 1996 Mar 28;66(1):124–129. [PubMed]
  • Chen IS, McLaughlin J, Gasson JC, Clark SC, Golde DW. Molecular characterization of genome of a novel human T-cell leukaemia virus. Nature. 1983 Oct 6;305(5934):502–505. [PubMed]
  • Cross SL, Feinberg MB, Wolf JB, Holbrook NJ, Wong-Staal F, Leonard WJ. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell. 1987 Apr 10;49(1):47–56. [PubMed]
  • Degitz K, Li LJ, Caughman SW. Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene. J Biol Chem. 1991 Jul 25;266(21):14024–14030. [PubMed]
  • Dezzutti CS, Rudolph DL, Dhawan S, Lal RB. Modulation of HTLV-II-associated spontaneous lymphocyte proliferation by beta 2 integrin CD11a/CD18 involves interaction with its cognate ligand, CD54. Cell Immunol. 1994 Jun;156(1):113–123. [PubMed]
  • Dezzutti CS, Rudolph DL, Lal RB. Infection with human T-lymphotropic virus types I and II results in alterations of cellular receptors, including the up-modulation of T-cell counterreceptors CD40, CD54, and CD80 (B7-1). Clin Diagn Lab Immunol. 1995 May;2(3):349–355. [PMC free article] [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. 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. [PMC free article] [PubMed]
  • Ejima E, Rosenblatt JD, Massari M, Quan E, Stephens D, Rosen CA, Prager D. Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins. Blood. 1993 Feb 15;81(4):1017–1024. [PubMed]
  • Franklin AA, Kubik MF, Uittenbogaard MN, Brauweiler A, Utaisincharoen P, Matthews MA, Dynan WS, Hoeffler JP, Nyborg JK. Transactivation by the human T-cell leukemia virus Tax protein is mediated through enhanced binding of activating transcription factor-2 (ATF-2) ATF-2 response and cAMP element-binding protein (CREB). J Biol Chem. 1993 Oct 5;268(28):21225–21231. [PubMed]
  • Fukudome K, Furuse M, Fukuhara N, Orita S, Imai T, Takagi S, Nagira M, Hinuma Y, Yoshie O. Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines. Int J Cancer. 1992 Sep 30;52(3):418–427. [PubMed]
  • Fukudome K, Furuse M, Imai T, Nishimura M, Takagi S, Hinuma Y, Yoshie O. Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells. J Virol. 1992 Mar;66(3):1394–1401. [PMC free article] [PubMed]
  • Gavalchin J, Fan N, Waterbury PG, Corbett E, Faldasz BD, Peshick SM, Poiesz BJ, Papsidero L, Lane MJ. Regional localization of the putative cell surface receptor for HTLV-I to human chromosome 17q23.2-17q25.3. Virology. 1995 Sep 10;212(1):196–203. [PubMed]
  • Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. [PubMed]
  • Ghosh D. Status of the transcription factors database (TFD). Nucleic Acids Res. 1993 Jul 1;21(13):3117–3118. [PMC free article] [PubMed]
  • Hara H, Morita M, Iwaki T, Hatae T, Itoyama Y, Kitamoto T, Akizuki S, Goto I, Watanabe T. Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis. J Exp Med. 1994 Sep 1;180(3):831–839. [PMC free article] [PubMed]
  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. [PMC free article] [PubMed]
  • Hiscott J, Petropoulos L, Lacoste J. Molecular interactions between HTLV-1 Tax protein and the NF-kappa B/kappa B transcription complex. Virology. 1995 Dec 1;214(1):3–11. [PubMed]
  • Hjelle B, Appenzeller O, Mills R, Alexander S, Torrez-Martinez N, Jahnke R, Ross G. Chronic neurodegenerative disease associated with HTLV-II infection. Lancet. 1992 Mar 14;339(8794):645–646. [PubMed]
  • Hurst HC, Jones NC. Identification of factors that interact with the E1A-inducible adenovirus E3 promoter. Genes Dev. 1987 Dec;1(10):1132–1146. [PubMed]
  • Ijichi S, Ramundo MB, Takahashi H, Hall WW. In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II). J Exp Med. 1992 Jul 1;176(1):293–296. [PMC free article] [PubMed]
  • Imai T, Fukudome K, Takagi S, Nagira M, Furuse M, Fukuhara N, Nishimura M, Hinuma Y, Yoshie O. C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63. J Immunol. 1992 Nov 1;149(9):2879–2886. [PubMed]
  • Imai T, Tanaka Y, Fukudome K, Takagi S, Araki K, Yoshie O. Enhanced expression of LFA-3 on human T-cell lines and leukemic cells carrying human T-cell-leukemia virus type 1. Int J Cancer. 1993 Nov 11;55(5):811–816. [PubMed]
  • Imai T, Yoshie O. C33 antigen and M38 antigen recognized by monoclonal antibodies inhibitory to syncytium formation by human T cell leukemia virus type 1 are both members of the transmembrane 4 superfamily and associate with each other and with CD4 or CD8 in T cells. J Immunol. 1993 Dec 1;151(11):6470–6481. [PubMed]
  • Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. [PMC free article] [PubMed]
  • Ishikawa T, Imura A, Tanaka K, Shirane H, Okuma M, Uchiyama T. E-selectin and vascular cell adhesion molecule-1 mediate adult T-cell leukemia cell adhesion to endothelial cells. Blood. 1993 Sep 1;82(5):1590–1598. [PubMed]
  • Iwasaki Y. Pathology of chronic myelopathy associated with HTLV-I infection (HAM/TSP). J Neurol Sci. 1990 Apr;96(1):103–123. [PubMed]
  • Iwasaki Y, Ohara Y, Kobayashi I, Akizuki S. Infiltration of helper/inducer T lymphocytes heralds central nervous system damage in human T-cell leukemia virus infection. Am J Pathol. 1992 May;140(5):1003–1008. [PMC free article] [PubMed]
  • Jacobson S, Lehky T, Nishimura M, Robinson S, McFarlin DE, Dhib-Jalbut S. Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis. Ann Neurol. 1993 Apr;33(4):392–396. [PubMed]
  • Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982 Nov 5;218(4572):571–573. [PubMed]
  • Kanamori H, Suzuki N, Siomi H, Nosaka T, Sato A, Sabe H, Hatanaka M, Honjo T. HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA. EMBO J. 1990 Dec;9(12):4161–4166. [PMC free article] [PubMed]
  • Kawasaki ES, Clark SS, Coyne MY, Smith SD, Champlin R, Witte ON, McCormick FP. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698–5702. [PMC free article] [PubMed]
  • Kim SJ, Kehrl JH, Burton J, Tendler CL, Jeang KT, Danielpour D, Thevenin C, Kim KY, Sporn MB, Roberts AB. Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia. J Exp Med. 1990 Jul 1;172(1):121–129. [PMC free article] [PubMed]
  • Kimata JT, Palker TJ, Ratner L. The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway. J Virol. 1993 Jun;67(6):3134–3141. [PMC free article] [PubMed]
  • Kinoshita T, Shimoyama M, Tobinai K, Ito M, Ito S, Ikeda S, Tajima K, Shimotohno K, Sugimura T. Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5620–5624. [PMC free article] [PubMed]
  • Lal RB, Mainolfi E, Rothlein R. Elevated levels of cICAM-1 in patients with human T-cell leukemia virus type I associated myelopathy and adult T-cell leukemia. Blood. 1992 Nov 1;80(9):2434–2435. [PubMed]
  • Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol. 1994 Jan;68(1):510–516. [PMC free article] [PubMed]
  • Makgoba MW, Sanders ME, Shaw S. The CD2-LFA-3 and LFA-1-ICAM pathways: relevance to T-cell recognition. Immunol Today. 1989 Dec;10(12):417–422. [PubMed]
  • Merl S, Kloster B, Moore J, Hubbell C, Tomar R, Davey F, Kalinowski D, Planas A, Ehrlich G, Clark D, et al. Efficient transformation of previously activated and dividing T lymphocytes by human T cell leukemia-lymphoma virus. Blood. 1984 Nov;64(5):967–974. [PubMed]
  • Montminy MR, Sevarino KA, Wagner JA, Mandel G, Goodman RH. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. [PMC free article] [PubMed]
  • Mori N, Murakami S, Oda S, Eto S. Human T-cell leukemia virus type I tax induces intracellular adhesion molecule-1 expression in T cells. Blood. 1994 Jul 1;84(1):350–351. [PubMed]
  • Nagata K, Ohtani K, Nakamura M, Sugamura K. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat. J Virol. 1989 Aug;63(8):3220–3226. [PMC free article] [PubMed]
  • Nakamura M, Niki M, Nagata K, Ohtani K, Saito S, Hinuma Y, Sugamura K. Cell line-dependent response of the enhancer element of simian virus 40 to transactivator p40tax encoded by human T-cell leukemia virus type I. J Biol Chem. 1989 Dec 5;264(34):20189–20192. [PubMed]
  • Nimer SD, Gasson JC, Hu K, Smalberg I, Williams JL, Chen IS, Rosenblatt JD. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene. 1989 Jun;4(6):671–676. [PubMed]
  • Ohtani K, Nakamura M, Saito S, Noda T, Ito Y, Sugamura K, Hinuma Y. Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression. EMBO J. 1987 Feb;6(2):389–395. [PMC free article] [PubMed]
  • Osame M, Matsumoto M, Usuku K, Izumo S, Ijichi N, Amitani H, Tara M, Igata A. Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells. Ann Neurol. 1987 Feb;21(2):117–122. [PubMed]
  • Parslow TG, Jones SD, Bond B, Yamamoto KR. The immunoglobulin octanucleotide: independent activity and selective interaction with enhancers. Science. 1987 Mar 20;235(4795):1498–1501. [PubMed]
  • Richardson JH, Edwards AJ, Cruickshank JK, Rudge P, Dalgleish AG. In vivo cellular tropism of human T-cell leukemia virus type 1. J Virol. 1990 Nov;64(11):5682–5687. [PMC free article] [PubMed]
  • Roe T, Reynolds TC, Yu G, Brown PO. Integration of murine leukemia virus DNA depends on mitosis. EMBO J. 1993 May;12(5):2099–2108. [PMC free article] [PubMed]
  • Rosenblatt JD, Golde DW, Wachsman W, Giorgi JV, Jacobs A, Schmidt GM, Quan S, Gasson JC, Chen IS. A second isolate of HTLV-II associated with atypical hairy-cell leukemia. N Engl J Med. 1986 Aug 7;315(6):372–377. [PubMed]
  • Sakamoto KM, Nimer SD, Rosenblatt JD, Gasson JC. HTLV-I and HTLV-II tax trans-activate the human EGR-1 promoter through different cis-acting sequences. Oncogene. 1992 Nov;7(11):2125–2130. [PubMed]
  • Seiki M, Hattori S, Hirayama Y, Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. [PMC free article] [PubMed]
  • Shah NP, Wachsman W, Cann AJ, Souza L, Slamon DJ, Chen IS. Comparison of the trans-activation capabilities of the human T-cell leukemia virus type I and II chi proteins. Mol Cell Biol. 1986 Nov;6(11):3626–3631. [PMC free article] [PubMed]
  • Shimotohno K, Takahashi Y, Shimizu N, Gojobori T, Golde DW, Chen IS, Miwa M, Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. [PMC free article] [PubMed]
  • Smith MR, Greene WC. Molecular biology of the type I human T-cell leukemia virus (HTLV-I) and adult T-cell leukemia. J Clin Invest. 1991 Mar;87(3):761–766. [PMC free article] [PubMed]
  • Sodroski J. The human T-cell leukemia virus (HTLV) transactivator (Tax) protein. Biochim Biophys Acta. 1992 Sep 14;1114(1):19–29. [PubMed]
  • Sommerfelt MA, Williams BP, Clapham PR, Solomon E, Goodfellow PN, Weiss RA. Human T cell leukemia viruses use a receptor determined by human chromosome 17. Science. 1988 Dec 16;242(4885):1557–1559. [PubMed]
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]
  • Takebe Y, Seiki M, Fujisawa J, Hoy P, Yokota K, Arai K, Yoshida M, Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. [PMC free article] [PubMed]
  • Tanaka Y, Fukudome K, Hayashi M, Takagi S, Yoshie O. Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines. Int J Cancer. 1995 Feb 8;60(4):554–561. [PubMed]
  • Uchijima M, Sato H, Fujii M, Seiki M. Tax proteins of human T-cell leukemia virus type 1 and 2 induce expression of the gene encoding erythroid-potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1). J Biol Chem. 1994 May 27;269(21):14946–14950. [PubMed]
  • Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed]
  • Wake A, Tanaka Y, Nakatsuka K, Misago M, Oda S, Morimoto I, Eto S. Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro. Blood. 1995 Sep 15;86(6):2257–2267. [PubMed]
  • Wucherpfennig KW, Höllsberg P, Richardson JH, Benjamin D, Hafler DA. T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2110–2114. [PMC free article] [PubMed]
  • Yoshida M. Expression of the HTLV-1 genome and its association with a unique T-cell malignancy. Biochim Biophys Acta. 1987 Jul 8;907(2):145–161. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...