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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 12, 2003 Accepted June 4, 2004 Transcriptional activation of hTERT through the NF-kB pathway in HTLV-I transformed cells Uma Sinha-Datta, Izumi Horikawa, Eriko Michishita, Abhik Datta, Janitzia C Sigler-Nicot, Megan Brown, Mirdad Kazanji, Carl J Barrett, and Christophe Nicot* * Corresponding author; email: cnicot{at}kumc.edu. In immortal cells 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 ATLL samples, but not asymptomatic carriers. Although Tax impaired induction of 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 NF-kB pathway. Consistently, Tax mutants inactive for NF-kB activation could not activate the hTERT nor 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-kB-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: J. M. Taylor, M. Brown, M. Nejmeddine, K. J. Kim, L. Ratner, M. Lairmore, and C. Nicot Novel Role for Interleukin-2 Receptor-Jak Signaling in Retrovirus Transmission J. Virol., November 15, 2009; 83(22): 11467 - 11476. [Abstract] [Full Text] [PDF] A. M. Gannon and B. T. Kinsella Regulation of the human thromboxane A2 receptor gene by Sp1, Egr1, NF-E2, GATA-1, and Ets-1 in megakaryocytes J. Lipid Res., December 1, 2008; 49(12): 2590 - 2604. [Abstract] [Full Text] [PDF] L. Terrin, J. Dal Col, E. Rampazzo, P. Zancai, M. Pedrotti, G. Ammirabile, S. Bergamin, S. Rizzo, R. Dolcetti, and A. De Rossi Latent Membrane Protein 1 of Epstein-Barr Virus Activates the hTERT Promoter and Enhances Telomerase Activity in B Lymphocytes J. Virol., October 15, 2008; 82(20): 10175 - 10187. [Abstract] [Full Text] [PDF] H. Ly Telomerase regulation in HTLV-I infection Blood, October 1, 2008; 112(7): 2603 - 2604. [Full Text] [PDF] M. Bellon and C. 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