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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2475-2483. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2003-10-3508. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3508v1 104/8/2475    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 Baran-Marszak, F. Articles by Fagard, R. Search for Related Content PubMed PubMed Citation Articles by Baran-Marszak, F. Articles by Fagard, R. Related Collections Immunobiology Neoplasia Apoptosis Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Differential roles of STAT1 and STAT1 in fludarabine-induced cell cycle arrest and apoptosis in human B cells Fanny Baran-Marszak, Jean Feuillard, Imen Najjar, Christophe Le Clorennec, Jean-Marie Béchet, Isabelle Dusanter-Fourt, Georg W. Bornkamm, Martine Raphaël, and Remi Fagard From the Equipe d'Accueil 3406 Université Paris 13, Service de Biochimie, Hôpital Avicenne, France; Unité Mixte de Recherche (UMR) Centre National de la Recherche Scientifique (CNRS) 6101 and Laboratoire d'Hématologie, Centre Hospitalier Universitaire (CHU) Dupuytren and Faculté de Médecine, Université de Limoges, France; Institut National de la Santé et de la Recherche Médicale (INSERM) E109, Université Paris 11, Kremlin-Bicêtre, France; UMR 6551, Université de Caen, France; Unité INSERM Institut Cochin de Génétique Moléculaire (ICGM) Cochin Port-Royal, France; and Forschungszentrum für Umwelt und Gesundheit (GSF)–Institute of Clinical Molecular Biology and Tumor Genetics, Munich, Germany. Signal transducer and activator of transcription 1 (STAT1), a transcription factor known to participate in antiviral responses, acts as a tumor suppressor inhibiting cell growth and promoting apoptosis. To study the role of STAT1 in DNA damage–induced apoptosis in B lymphocytes, its active form, STAT1, was specifically inhibited by the overexpression of STAT1, the STAT1 truncated inhibitory isoform. An episomal vector with a tetracycline-inducible bidirectional promoter was created to induce the expression of 2 proteins, STAT1 and enhanced green fluorescence protein (EGFP). The same vector was used to overexpress STAT1 as a control. Expression of STAT1 inhibited the phosphorylation, the DNA-binding activity, and the transcriptional activity of STAT1, as well as the expression of STAT1 target genes such as p21WAF1/CIP1, TAP1, IRF1, and PKR. Inhibiting STAT1 by STAT1 increased the growth rate of transfected cells and their resistance to fludarabine-induced apoptosis and cell cycle arrest. Overexpressing STAT1 reversed the negative regulation of Mdm2 expression observed after treatment with interferon-gamma (IFN-), which activates STAT1, or with fludarabine. Nuclear translocation of p53 after fludarabine treatment was decreased when STAT1 was overexpressed, and it was increased when STAT1 was induced. Oligonucleotide pull-down experiments showed a physical STAT1/p53 interaction. Our results show that imbalance between the antiproliferative/proapoptotic isoform STAT1 and the proliferative isoform STAT1 is likely to play a crucial role in the regulation of proliferation and apoptosis and that STAT1 may regulate p53 activity and sensitize B cells to fludarabine-induced apoptosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Faumont, C. Le Clorennec, P. Teira, G. Goormachtigh, J. Coll, Y. Canitrot, C. Cazaux, J.-S. Hoffmann, P. Brousset, G. Delsol, et al. Regulation of DNA Polymerase {beta} by the LMP1 Oncoprotein of EBV through the Nuclear Factor-{kappa}B Pathway Cancer Res., June 15, 2009; 69(12): 5177 - 5185. [Abstract] [Full Text] [PDF] N. Faumont, S. Durand-Panteix, M. Schlee, S. Gromminger, M. Schuhmacher, M. Holzel, G. Laux, R. Mailhammer, A. Rosenwald, L. M. Staudt, et al. c-Myc and Rel/NF-{kappa}B Are the Two Master Transcriptional Systems Activated in the Latency III Program of Epstein-Barr Virus-Immortalized B Cells J. Virol., May 15, 2009; 83(10): 5014 - 5027. [Abstract] [Full Text] [PDF] N. Jandu, Z. J. Zeng, K. C. Johnson-Henry, and P. M. Sherman Probiotics prevent enterohaemorrhagic Escherichia coli O157 : H7-mediated inhibition of interferon-{gamma}-induced tyrosine phosphorylation of STAT-1 Microbiology, February 1, 2009; 155(2): 531 - 540. [Abstract] [Full Text] [PDF] I. Najjar, P. O. Schischmanoff, F. Baran-Marszak, P.-A. Deglesne, I. Youlyouz-Marfak, M. Pampin, J. Feuillard, G. W. Bornkamm, M. K. Chelbi-Alix, and R. Fagard Novel function of STAT1{beta} in B cells: induction of cell death by a mechanism different from that of STAT1{alpha} J. Leukoc. Biol., December 1, 2008; 84(6): 1604 - 1612. [Abstract] [Full Text] [PDF] D. Verma and S. Swaminathan Epstein-Barr Virus SM Protein Functions as an Alternative Splicing Factor J. Virol., July 15, 2008; 82(14): 7180 - 7188. [Abstract] [Full Text] [PDF] C. Le Clorennec, T.-S. Ouk, I. Youlyouz-Marfak, S. Panteix, C.-C. Martin, J. Rastelli, E. Adriaenssens, U. Zimber-Strobl, J. Coll, J. Feuillard, et al. Molecular Basis of Cytotoxicity of Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) in EBV Latency III B Cells: LMP1 Induces Type II Ligand-Independent Autoactivation of CD95/Fas with Caspase 8-Mediated Apoptosis J. Virol., July 1, 2008; 82(13): 6721 - 6733. [Abstract] [Full Text] [PDF] C. Le Clorennec, I. Youlyouz-Marfak, E. Adriaenssens, J. Coll, G. W. Bornkamm, and J. Feuillard EBV latency III immortalization program sensitizes B cells to induction of CD95-mediated apoptosis via LMP1: role of NF-{kappa}B, STAT1, and p53 Blood, March 1, 2006; 107(5): 2070 - 2078. [Abstract] [Full Text] [PDF] I. Najjar, F. Baran-Marszak, C. Le Clorennec, C. Laguillier, O. Schischmanoff, I. Youlyouz-Marfak, M. Schlee, G. W. Bornkamm, M. Raphael, J. Feuillard, et al. Latent Membrane Protein 1 Regulates STAT1 through NF-{kappa}B-Dependent Interferon Secretion in Epstein-Barr Virus-Immortalized B Cells J. Virol., April 15, 2005; 79(8): 4936 - 4943. [Abstract] [Full Text] [PDF]

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