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PMID: 8642682 Published · ppublish English Journal Article

Human T-cell lymphotropic virus type 1 Tax1 activation of NF-kappa B: involvement of the protein kinase C pathway.

Journal of virology ·Vol. 70 ·No. 4 ·1996-04-00 ·Pages 2525-32

Lindholm PF, Tamami M, Makowski J, Brady JN

Abstract

Human T-cell lymphotropic virus type 1 Tax1 induces the activation and nuclear localization of the cellular transcription factor, NF-kappa B. Treatment of cells with calphostin C, a protein kinase C (PKC) inhibitor, blocked induction of NF-kappa B DNA binding activity in human T-cell lymphotropic virus type 1-transformed C81 cells and Tax1-stimulated murine pre-B cells, suggesting that PKC was an important intermediate in the NF-kappa B induction pathway. We further demonstrate that Tax1 associates with, and activates, PKC. PKC was coimmunoprecipitated with anti- Tax1 sera from Tax1-expressing MT4 extracts and Jurkat extracts in the presence of exogenous Tax1 protein. In addition, the glutathione-S-transferase-Tax1 protein bound specifically to the alpha, delta, and eta PKC isoenzymes synthesized in rabbit reticulocyte lysates. The addition of Tax1 to in vitro kinase reaction mixtures leads to the phosphorylation of Tax1 and an 18-fold increase in the autophosphorylation of PKC. Transfection of Jurkat cells with wild-type Tax1 stimulated membrane translocation of PKC. In contrast, Tax1 mutant M22, which fails to stimulate NF-kappa B-dependent transcription, failed to stimulate membrane translocation of PKC. Tax1 did not directly increase PKC phosphorylation of I kappa B alpha. Our results are consistent with a model in which Tax1 interacts with PKC and stimulates membrane translocation and triggering of the PKC pathway. Subsequent steps in the PKC cascade likely stimulate phosphorylation of I kappa B alpha.

MeSH Terms
Animals Base Sequence Cell Line Cell Membrane/enzymology DNA, Viral Enzyme Inhibitors/pharmacology Gene Products, tax/genetics,physiology Human T-lymphotropic virus 1/genetics,physiology Humans Mice Mice, Inbred C57BL Mice, Inbred DBA Molecular Sequence Data NF-kappa B/biosynthesis Naphthalenes/pharmacology Phosphorylation Protein Binding Protein Biosynthesis Protein Kinase C/antagonists & inhibitors,metabolism Proto-Oncogene Proteins/metabolism Transcription Factor RelB Transcription Factors Transfection
Chemicals
DNA, Viral Enzyme Inhibitors Gene Products, tax NF-kappa B Naphthalenes Proto-Oncogene Proteins RELB protein, human Relb protein, mouse Transcription Factors Transcription Factor RelB Protein Kinase C calphostin C
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lindholm P F
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892-5005, USA.
Tamami M
Makowski J
Brady J N
References (82)
82 references, click to expand
  1. Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I.
    Proc Natl Acad Sci U S A. 1988 Oct;85(19):7124-8 PMID: 3174625
  2. Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro.
    Blood. 1989 Jan;73(1):194-201 PMID: 2783372
  3. Response of the human T-cell leukemia virus type 1 long terminal repeat to cyclic AMP.
    J Virol. 1989 Apr;63(4):1604-11 PMID: 2538645
  4. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336-40 PMID: 2494664
  5. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C.
    Biochem Biophys Res Commun. 1989 Mar 15;159(2):548-53 PMID: 2467670
  6. Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA).
    EMBO J. 1988 Dec 20;7(13):4221-9 PMID: 3072196
  7. Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences.
    J Virol. 1989 Jul;63(7):2987-94 PMID: 2786091
  8. Purification and characterization of multiple nuclear factors that bind to the TAX-inducible enhancer within the human T-cell leukemia virus type 1 long terminal repeat.
    Mol Cell Biol. 1989 Apr;9(4):1733-45 PMID: 2786141
  9. 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):3220-6 PMID: 2501514
  10. Utilization of signal transduction pathway by the human T-cell leukemia virus type I transcriptional activator tax.
    J Virol. 1989 Sep;63(9):3761-8 PMID: 2474673
  11. Inhibition of protein kinase C by calphostin C is light-dependent.
    Biochem Biophys Res Commun. 1991 Apr 15;176(1):288-93 PMID: 1708246
  12. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity.
    Cell. 1991 Jun 28;65(7):1281-9 PMID: 1829648
  13. The indirect association of human T-cell leukemia virus tax protein with DNA results in transcriptional activation.
    J Virol. 1991 Aug;65(8):4525-8 PMID: 2072462
  14. Induction of nuclear NF-kappa B DNA binding activity after exposure of lymphoid cells to soluble tax1 protein.
    New Biol. 1990 Nov;2(11):1034-43 PMID: 2101630
  15. Intracellular receptors for activated protein kinase C. Identification of a binding site for the enzyme.
    J Biol Chem. 1991 Aug 15;266(23):14866-8 PMID: 1831196
  16. NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I.
    Virology. 1991 Oct;184(2):553-62 PMID: 1679576
  17. Complexities of the protein kinase C pathway.
    Mol Carcinog. 1991;4(5):339-44 PMID: 1910477
  18. Transactivation of Krox-20 and Krox-24 promoters by the HTLV-1 Tax protein through common regulatory elements.
    Oncogene. 1991 Oct;6(10):1851-7 PMID: 1833716
  19. Twenty-one base pair repeat elements influence the ability of a Gal4-Tax fusion protein to transactivate the HTLV-I long terminal repeat.
    Virology. 1993 Aug;195(2):569-77 PMID: 8337832
  20. Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes.
    Blood. 1993 Aug 15;82(4):1212-20 PMID: 8353285
  21. Interleukin-1-induced signaling in T-cells. Evidence for the involvement of phosphatases PP1 and PP2A in regulating protein kinase C-mediated protein phosphorylation and interleukin-2 synthesis.
    J Biol Chem. 1993 Oct 5;268(28):21066-72 PMID: 8407943
  22. Stabilization of wild-type p53 in human T-lymphocytes transformed by HTLV-I.
    Oncogene. 1993 Nov;8(11):3029-36 PMID: 8414503
  23. HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization.
    Science. 1993 Oct 15;262(5132):395-9 PMID: 8211160
  24. In vivo control of NF-kappa B activation by I kappa B alpha.
    EMBO J. 1993 Dec;12(12):4685-95 PMID: 8223478
  25. Protein kinase C-mediated bidirectional regulation of DNA synthesis, RB protein phosphorylation, and cyclin-dependent kinases in human vascular endothelial cells.
    J Biol Chem. 1993 Nov 5;268(31):23041-8 PMID: 8226819
  26. Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3584-8 PMID: 8170951
  27. Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B.
    Mol Cell Biol. 1994 Oct;14(10):6443-51 PMID: 7935369
  28. Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene.
    Mol Cell Biol. 1994 Nov;14(11):7377-84 PMID: 7935451
  29. In vivo regulation of protein kinase C by trans-phosphorylation followed by autophosphorylation.
    J Biol Chem. 1994 Nov 25;269(47):29359-62 PMID: 7961910
  30. Constitutive phosphorylation and turnover of I kappa B alpha in human T-cell leukemia virus type I-infected and Tax-expressing T cells.
    J Virol. 1995 Jan;69(1):564-9 PMID: 7983756
  31. The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway.
    Virology. 1990 May;176(1):126-32 PMID: 1970444
  32. HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element.
    J Biol Chem. 1989 Sep 15;264(26):15236-41 PMID: 2768259
  33. trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene.
    Mol Cell Biol. 1989 Nov;9(11):4731-7 PMID: 2689863
  34. A mutant protein kinase C that can transform fibroblasts.
    Nature. 1989 Dec 14;342(6251):807-11 PMID: 2601739
  35. A point mutation at the putative ATP-binding site of protein kinase C alpha abolishes the kinase activity and renders it down-regulation-insensitive. A molecular link between autophosphorylation and down-regulation.
    J Biol Chem. 1990 Apr 15;265(11):6296-300 PMID: 2318854
  36. Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C.
    EMBO J. 1990 Apr;9(4):1165-70 PMID: 2182321
  37. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor.
    Mol Cell Biol. 1990 May;10(5):2327-34 PMID: 2183031
  38. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B.
    Nature. 1990 Apr 12;344(6267):678-82 PMID: 2157987
  39. Interaction of host cell proteins with the human T-cell leukemia virus type I transcriptional control region. II. A comprehensive map of protein-binding sites facilitates construction of a simple chimeric promoter responsive to the viral tax2 gene product.
    J Biol Chem. 1990 May 15;265(14):8237-42 PMID: 2186038
  40. Protein kinase inhibitor H-7 blocks accumulation of unspliced mRNA of human T-cell leukemia virus type I (HTLV-I).
    Biochem Biophys Res Commun. 1990 Jun 15;169(2):469-75 PMID: 2357216
  41. Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):5218-22 PMID: 2367534
  42. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain.
    EMBO J. 1990 Aug;9(8):2537-42 PMID: 2196176
  43. A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat.
    Mol Cell Biol. 1990 Aug;10(8):4192-201 PMID: 2370863
  44. Autophosphorylation of protein kinase C at three separated regions of its primary sequence.
    Science. 1990 Jul 27;249(4967):408-11 PMID: 2377895
  45. Direct and cytokine-mediated activation of protein kinase C induces human immunodeficiency virus expression in chronically infected promonocytic cells.
    J Virol. 1990 Sep;64(9):4306-12 PMID: 2200885
  46. Phosphatidylserine affects specificity of protein kinase C substrate phosphorylation and autophosphorylation.
    Biochemistry. 1990 Jul 17;29(28):6656-61 PMID: 2397206
  47. Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.
    J Virol. 1990 Nov;64(11):5412-9 PMID: 1976820
  48. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943-7 PMID: 2263644
  49. Distinct mechanisms of regulation of protein kinase C epsilon by hormones and phorbol diesters.
    J Biol Chem. 1991 Jan 5;266(1):168-73 PMID: 1985890
  50. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes.
    Genes Dev. 1990 Nov;4(11):1875-85 PMID: 2276622
  51. Binding of the HTLV-I Tax1 transactivator to the inducible 21 bp enhancer is mediated by the cellular factor HEB1.
    EMBO J. 1991 Dec;10(12):3795-803 PMID: 1935901
  52. 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
  53. Purified I kappa B-beta is inactivated upon dephosphorylation.
    J Biol Chem. 1992 Jan 5;267(1):239-46 PMID: 1309735
  54. Hepatitis B virus X protein activates transcription factor NF-kappa B without a requirement for protein kinase C.
    J Virol. 1992 Feb;66(2):983-91 PMID: 1309924
  55. Extracellular Tax1 protein stimulates tumor necrosis factor-beta and immunoglobulin kappa light chain expression in lymphoid cells.
    J Virol. 1992 Mar;66(3):1294-302 PMID: 1738191
  56. Inhibition of protein kinase C results in decreased expression of bovine leukemia virus.
    J Virol. 1992 Jul;66(7):4427-33 PMID: 1318412
  57. Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B.
    J Biol Chem. 1992 Aug 15;267(23):16288-91 PMID: 1644814
  58. Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105.
    Oncogene. 1992 Sep;7(9):1737-42 PMID: 1501885
  59. The protein kinase C family.
    Eur J Biochem. 1992 Sep 15;208(3):547-57 PMID: 1396661
  60. Role of cadmium in activating nuclear protein kinase C and the enzyme binding to nuclear protein.
    J Biol Chem. 1992 Oct 5;267(28):19824-8 PMID: 1400297
  61. Antioxidants selectively suppress activation of NF-kappa B by human T-cell leukemia virus type I Tax protein.
    J Virol. 1992 Nov;66(11):6288-93 PMID: 1404592
  62. Altered expression of protein kinase C in adult T-cell leukemia cells.
    Int J Hematol. 1992 Oct;56(2):135-41 PMID: 1421175
  63. Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11627-31 PMID: 1454855
  64. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway.
    Science. 1993 Mar 26;259(5103):1912-5 PMID: 8096091
  65. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532-6 PMID: 8460169
  66. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation.
    Mol Cell Biol. 1993 Jun;13(6):3301-10 PMID: 8497253
  67. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells.
    J Biol Chem. 1993 Jun 5;268(16):11803-10 PMID: 8505309
  68. Phorbol esters modulate the phosphorylation of human T-cell leukemia virus type I Tax.
    J Virol. 1993 Jul;67(7):4436-41 PMID: 8510230
  69. Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells.
    New Biol. 1989 Dec;1(3):275-84 PMID: 2487294
  70. Induction of the HTLV-I LTR by Jun occurs through the Tax-responsive 21-bp elements.
    Virology. 1991 Mar;181(1):218-27 PMID: 1899734
  71. Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties.
    J Biol Chem. 1982 Nov 25;257(22):13341-8 PMID: 7142151
  72. Restricted expression of human T-cell leukemia--lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes.
    Virology. 1983 Aug;129(1):51-64 PMID: 6412453
  73. Calcium pools in saponin-permeabilized guinea pig hepatocytes.
    J Biol Chem. 1983 Dec 25;258(24):15336-45 PMID: 6654915
  74. The role of protein kinase C in cell surface signal transduction and tumour promotion.
    Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
  75. Interaction of protein kinase C with membranes is regulated by Ca2+, phorbol esters, and ATP.
    J Biol Chem. 1985 Dec 15;260(29):15718-22 PMID: 4066694
  76. Early signals in the mitogenic response.
    Science. 1986 Oct 10;234(4773):161-6 PMID: 3018928
  77. 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
  78. Identification of p40x-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat.
    J Virol. 1987 Jul;61(7):2175-81 PMID: 3035218
  79. Overproduction of protein kinase C causes disordered growth control in rat fibroblasts.
    Cell. 1988 Feb 12;52(3):343-54 PMID: 3345563
  80. Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA.
    Cell. 1988 Feb 12;52(3):447-58 PMID: 3162207
  81. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor.
    Nature. 1988 Jun 23;333(6175):776-8 PMID: 2838755
  82. 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
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.70.4.2525-2532.1996
Published
1996-04-00
Pages
2525-32
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190098
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.70.4.2525-2532.1996 PMC Full Text View journal details
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