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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2523-2531. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2003-12-4251. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4251v1 104/8/2523    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sinha-Datta, U. Articles by Nicot, C. Search for Related Content PubMed PubMed Citation Articles by Sinha-Datta, U. Articles by Nicot, C. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Transcriptional activation of hTERT through the NF-B pathway in HTLV-I–transformed cells Uma Sinha-Datta, Izumi Horikawa, Eriko Michishita, Abhik Datta, Janitzia C. Sigler-Nicot, Megan Brown, Mirdad Kazanji, J. Carl Barrett, and 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. 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 B (NF-B) pathway. Consistently, Tax mutants inactive for NF-B 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-B–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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Bellon and C. Nicot Central role of PI3K in transcriptional activation of hTERT in HTLV-I-infected cells Blood, October 1, 2008; 112(7): 2946 - 2955. [Abstract] [Full Text] [PDF] M. Bellon and C. Nicot Regulation of Telomerase and Telomeres: Human Tumor Viruses Take Control J Natl Cancer Inst, January 16, 2008; 100(2): 98 - 108. [Abstract] [Full Text] [PDF] Q. Yang, R. Zhang, I. Horikawa, K. Fujita, Y. Afshar, A. Kokko, P. Laiho, L. A. Aaltonen, and C. C. Harris Functional Diversity of Human Protection of Telomeres 1 Isoforms in Telomere Protection and Cellular Senescence Cancer Res., December 15, 2007; 67(24): 11677 - 11686. [Abstract] [Full Text] [PDF] G P Taylor Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma J. Clin. Pathol., December 1, 2007; 60(12): 1392 - 1396. [Abstract] [Full Text] [PDF] U. Sinha-Datta, A. Datta, S. Ghorbel, M. D. Dodon, and C. Nicot Human T-cell Lymphotrophic Virus Type I Rex and p30 Interactions Govern the Switch between Virus Latency and Replication J. Biol. Chem., May 11, 2007; 282(19): 14608 - 14615. [Abstract] [Full Text] [PDF] S. Ghorbel, U. Sinha-Datta, M. Dundr, M. Brown, G. Franchini, and C. Nicot Human T-cell Leukemia Virus Type I p30 Nuclear/Nucleolar Retention Is Mediated through Interactions with RNA and a Constituent of the 60 S Ribosomal Subunit J. Biol. Chem., December 1, 2006; 281(48): 37150 - 37158. [Abstract] [Full Text] [PDF] A. Datta, M. Bellon, U. Sinha-Datta, A. Bazarbachi, Y. Lepelletier, D. Canioni, T. A. Waldmann, O. Hermine, and C. Nicot Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence Blood, August 1, 2006; 108(3): 1021 - 1029. [Abstract] [Full Text] [PDF] T. Braun, G. Carvalho, A. Coquelle, M.-C. Vozenin, P. Lepelley, F. Hirsch, J.-J. Kiladjian, V. Ribrag, P. Fenaux, and G. Kroemer NF-{kappa}B constitutes a potential therapeutic target in high-risk myelodysplastic syndrome Blood, February 1, 2006; 107(3): 1156 - 1165. [Abstract] [Full Text] [PDF] E. Michishita, J. Y. Park, J. M. Burneskis, J. C. Barrett, and I. Horikawa Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins Mol. Biol. Cell, October 1, 2005; 16(10): 4623 - 4635. [Abstract] [Full Text] [PDF] Y. Matsumura-Arioka, K. Ohtani, T. Hara, R. Iwanaga, and M. Nakamura Identification of two distinct elements mediating activation of telomerase (hTERT) gene expression in association with cell growth in human T cells Int. Immunol., February 1, 2005; 17(2): 207 - 215. [Abstract] [Full Text] [PDF]

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