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PMID: 11861831 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Human T-cell leukemia virus type 2 (HTLV-2) Tax protein transforms a rat fibroblast cell line but less efficiently than HTLV-1 Tax.

Journal of virology ·Vol. 76 ·No. 6 ·2002-03-00 ·Pages 2648-53

Endo K, Hirata A, Iwai K, Sakurai M, Fukushi M, Oie M, Higuchi M, Hall WW, Gejyo F, Fujii M

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are retroviruses with similar biological properties. Whereas HTLV-1 is the causative agent of an aggressive T-cell leukemia, HTLV-2 has been associated with only a few cases of lymphoproliferative disorders. Tax1 and Tax2 are the transcriptional activators of HTLV-1 and HTLV-2, respectively. Here we show that Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were lower than those of Tax1. Use of a chimeric Tax protein showed that the C-terminal amino acids 300 to 353 were responsible for the high transforming activity of Tax1. Activation of cellular genes by Tax1 through transcription factor NF-kappa B is reportedly essential for the transformation of Rat-1 cells. Tax2 also activated the transcription through NF-kappa B in Rat-1 cells, and such activity was equivalent to that induced by Tax1. Thus, the high transforming activity of Tax1 is mediated by mechanisms other than NF-kappa B activation. Our results showed that Tax2 has a lower transforming activity than Tax1 and suggest that the high transforming activity of Tax1 is involved in the leukemogenic property of HTLV-1.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cell Transformation, Viral Fibroblasts Gene Products, tax/chemistry,genetics,physiology Human T-lymphotropic virus 2/physiology Humans Molecular Sequence Data Rats Transfection
Chemicals
Gene Products, tax
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Endo Keiichi
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
Hirata Akira
Iwai Kousuke
Sakurai Mamoru
Fukushi Masaya
Oie Masayasu
Higuchi Masaya
Hall William W
Gejyo Fumitake
Fujii Masahiro
References (62)
62 references, click to expand
  1. HTLV-I and HTLV-II Tax: differences in induction of micronuclei in cells and transcriptional activation of viral LTRs.
    Virology. 1996 Mar 1;217(1):373-9 PMID: 8599225
  2. IKKgamma serves as a docking subunit of the IkappaB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein.
    J Biol Chem. 1999 Aug 13;274(33):22911-4 PMID: 10438454
  3. Identification and characterization of a new and distinct molecular subtype of human T-cell lymphotropic virus type 2.
    J Virol. 1996 Mar;70(3):1481-92 PMID: 8627666
  4. Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1/Cip1/Sdi1.
    Oncogene. 1996 Apr 18;12(8):1645-52 PMID: 8622884
  5. Aberrant expression and function of p53 in T-cells immortalized by HTLV-I Tax1.
    FEBS Lett. 1997 Apr 14;406(3):263-6 PMID: 9136898
  6. Human T-cell leukemia virus type 1 Tax protein transforms rat fibroblasts via two distinct pathways.
    J Virol. 1997 Jun;71(6):4445-51 PMID: 9151835
  7. Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes.
    Oncogene. 1997 May 1;14(17):2071-8 PMID: 9160887
  8. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11612-6 PMID: 9326658
  9. Mutational analysis of human T-cell leukemia virus type 2 Tax.
    J Virol. 1997 Nov;71(11):8912-7 PMID: 9343258
  10. Inhibition of p53 transactivation function by the human T-cell lymphotropic virus type 1 Tax protein.
    J Virol. 1998 Feb;72(2):1165-70 PMID: 9445014
  11. The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins.
    Oncogene. 1998 Feb 5;16(5):643-54 PMID: 9482110
  12. Human T-cell leukemia virus type 1 Tax protein induces the expression of lymphocyte chemoattractant SDF-1/PBSF.
    Virology. 1998 Feb 15;241(2):298-303 PMID: 9499804
  13. A human T-cell leukemia virus Tax variant incapable of activating NF-kappaB retains its immortalizing potential for primary T-lymphocytes.
    J Biol Chem. 1998 Mar 20;273(12):6698-703 PMID: 9506967
  14. HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation.
    Cell. 1998 May 29;93(5):875-84 PMID: 9630230
  15. The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta.
    J Biol Chem. 1998 Jun 26;273(26):15891-4 PMID: 9632633
  16. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation.
    Cell. 1998 Jun 26;93(7):1231-40 PMID: 9657155
  17. Tax oncoprotein of HTLV-1 binds to the human homologue of Drosophila discs large tumor suppressor protein, hDLG, and perturbs its function in cell growth control.
    Oncogene. 1999 Oct 28;18(44):5967-72 PMID: 10557085
  18. Human T-cell leukemia virus type 2 tax mutants that selectively abrogate NFkappaB or CREB/ATF activation fail to transform primary human T cells.
    J Virol. 2000 Mar;74(6):2655-62 PMID: 10684280
  19. Isolation, cloning, and complete nucleotide sequence of a phenotypically distinct Brazilian isolate of human T-lymphotropic virus type II (HTLV-II).
    Virology. 2000 May 25;271(1):142-54 PMID: 10814579
  20. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.
    Annu Rev Immunol. 2001;19:475-96 PMID: 11244044
  21. Adult T-cell leukemia: clinical and hematologic features of 16 cases.
    Blood. 1977 Sep;50(3):481-92 PMID: 301762
  22. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.
    Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9 PMID: 6261256
  23. 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):6476-80 PMID: 7031654
  24. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells.
    Nature. 1981 Dec 24;294(5843):770-1 PMID: 6275274
  25. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line.
    Science. 1982 Aug 20;217(4561):737-9 PMID: 6980467
  26. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  27. Molecular characterization of genome of a novel human T-cell leukaemia virus.
    Nature. 1983 Oct 6-12;305(5934):502-5 PMID: 6312323
  28. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells.
    Science. 1984 Jul 27;225(4660):381-5 PMID: 6330891
  29. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II.
    Science. 1984 Oct 5;226(4670):61-5 PMID: 6089351
  30. Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor.
    Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277-81 PMID: 2986109
  31. 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):3101-5 PMID: 2582407
  32. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats.
    Science. 1985 Aug 16;229(4714):675-9 PMID: 2992082
  33. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator.
    EMBO J. 1986 Mar;5(3):561-5 PMID: 3011413
  34. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1.
    EMBO J. 1986 Nov;5(11):2883-8 PMID: 3024966
  35. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering.
    Cell. 1987 Jan 30;48(2):343-50 PMID: 3026643
  36. 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 PMID: 3030566
  37. The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice.
    Science. 1987 Sep 11;237(4820):1324-9 PMID: 2888190
  38. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product.
    Science. 1988 Jul 1;241(4861):89-92 PMID: 2838905
  39. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene.
    Science. 1988 Sep 23;241(4873):1652-5 PMID: 2843985
  40. Identification of a cis-regulatory element involved in accumulation of human T-cell leukemia virus type II genomic mRNA.
    J Virol. 1988 Dec;62(12):4445-51 PMID: 2846863
  41. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526-30 PMID: 2847164
  42. Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro.
    Proc Natl Acad Sci U S A. 1990 Feb;87(3):1071-5 PMID: 2300570
  43. HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene.
    Science. 1990 Mar 2;247(4946):1082-4 PMID: 2309119
  44. Production of a recombinant human T-cell leukemia virus type-I trans-activator (tax1) antigen and its utilization for generation of monoclonal antibodies against various epitopes on the tax1 antigen.
    Int J Cancer. 1991 Jun 19;48(4):623-30 PMID: 1710610
  45. HTLV-1 Tax induces expression of various immediate early serum responsive genes.
    Oncogene. 1991 Jun;6(6):1023-9 PMID: 1906155
  46. Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway.
    J Clin Invest. 1991 Sep;88(3):1038-42 PMID: 1832173
  47. Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of kappa B enhancer-binding proteins: evidence for a pretranslational component of regulation.
    J Virol. 1991 Dec;65(12):6892-9 PMID: 1719236
  48. Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture.
    J Virol. 1992 Jul;66(7):4570-5 PMID: 1351105
  49. Proliferative response of Tax1-transduced primary human T cells to anti-CD3 antibody stimulation by an interleukin-2-independent pathway.
    J Virol. 1993 Mar;67(3):1211-7 PMID: 8437212
  50. Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax.
    J Virol. 1999 Oct;73(10):7981-7 PMID: 10482545
  51. Transcriptional up-regulation of the cyclin D2 gene and acquisition of new cyclin-dependent kinase partners in human T-cell leukemia virus type 1-infected cells.
    J Virol. 1999 Dec;73(12):9917-27 PMID: 10559304
  52. Human T-cell leukemia virus type 1 Tax activates transcription of the human fra-1 gene through multiple cis elements responsive to transmembrane signals.
    J Virol. 1993 Dec;67(12):7001-7 PMID: 8230424
  53. Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses.
    J Virol. 1995 Feb;69(2):1328-33 PMID: 7815516
  54. Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1057-61 PMID: 7862633
  55. NF-kappaB-inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax-mediated NF-kappaB activation.
    J Biol Chem. 1998 Aug 14;273(33):21132-6 PMID: 9694868
  56. Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.
    Mol Cell Biol. 1998 Sep;18(9):5157-65 PMID: 9710600
  57. Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line.
    J Virol. 1999 Feb;73(2):1271-7 PMID: 9882331
  58. Immortalization of CD4(+) and CD8(+) T lymphocytes by human T-cell leukemia virus type 1 Tax mutants expressed in a functional molecular clone.
    J Virol. 1999 Jun;73(6):4856-65 PMID: 10233947
  59. IKKgamma mediates the interaction of cellular IkappaB kinases with the tax transforming protein of human T cell leukemia virus type 1.
    J Biol Chem. 1999 May 28;274(22):15297-300 PMID: 10336413
  60. Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma.
    J Biol Chem. 1999 Jun 18;274(25):17402-5 PMID: 10364167
  61. Down-regulation of the INK4 family of cyclin-dependent kinase inhibitors by tax protein of HTLV-1 through two distinct mechanisms.
    Virology. 1999 Jul 5;259(2):384-91 PMID: 10388662
  62. Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.
    EMBO J. 1996 Feb 15;15(4):873-87 PMID: 8631308
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.6.2648-2653.2002
Published
2002-03-00
Pages
2648-53
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC135979
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.76.6.2648-2653.2002 PMC Full Text View journal details
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