Transcriptional activation of hTERT through the NF-κB pathway in HTLV-I–transformed cells

DOI PDF 被引用文献9件
  • Uma Sinha-Datta
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Izumi Horikawa
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Eriko Michishita
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Abhik Datta
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Janitzia C. Sigler-Nicot
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Megan Brown
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Mirdad Kazanji
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • J. Carl Barrett
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Christophe Nicot
    From the Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS; the Department of Obstetrics/Gynecology, Division of Reproductive Biology and Vaccine Research Peptide and Protein Engineering Laboratory, Ohio State University, Columbus, OH; and the Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.

抄録

<jats:title>Abstract</jats:title><jats:p>In immortal cells, the existence of a mechanism for the maintenance of telomere length is critical. In most cases this is achieved by the reactivation of telomerase, a cellular reverse transcriptase that prevents telomere shortening. Here we report that the telomerase gene (hTERT) promoter is up-regulated during transmission of human T-cell lymphotropic virus type-I (HTLV-I) to primary T cells in vitro and in ex vivo adult T-cell leukemia/lymphoma (ATLL) samples, but not asymptomatic carriers. Although Tax impaired induction of human telomerase reverse transcriptase (hTERT) mRNA in response to mitogenic stimulation, transduction of Tax into primary lymphocytes was sufficient to activate and maintain telomerase expression and telomere length when cultured in the absence of any exogenous stimulation. Transient transfection assays revealed that Tax stimulates the hTERT promoter through the nuclear factor κB (NF-κB) pathway. Consistently, Tax mutants inactive for NF-κB activation could not activate the hTERT or sustain telomere length in transduced primary lymphocytes. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays suggested that an increased binding of c-Myc and Sp1 is involved in the NF-κB–mediated activation of the hTERT promoter. This study establishes the role of Tax in regulation of telomerase expression, which may cooperate with other functions of Tax to promote HTLV-I–associated adult T-cell leukemia.</jats:p>

収録刊行物

  • Blood

    Blood 104 (8), 2523-2531, 2004-10-15

    American Society of Hematology

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