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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4021-4029. Prepublished online as a Blood First Edition Paper on January 19, 2006; DOI 10.1182/blood-2005-09-3572. This Article Full Text (PDF) All Versions of this Article: 2005-09-3572v1 107/10/4021    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 Nasr, R. Articles by Bazarbachi, A. Search for Related Content PubMed PubMed Citation Articles by Nasr, R. Articles by Bazarbachi, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2005 Accepted December 29, 2005 Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-B activation Rihab Nasr, Estelle Chiari, Marwan El-Sabban, Renaud Mahieux, Youmna Kfoury, Maher Abdulhay, Victor Yazbeck, Olivier Hermine, Hugues de The, Claudine Pique, and Ali Bazarbachi* Department of Internal Medicine, American University of Beirut, Beirut, Lebanon UMR 7151 CNRS/University of Paris, Paris, France Department of Human Morphology, University of Beirut, Beirut, Lebanon EPVO, Institut Pasteur, Paris, France CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France * Corresponding author; email: bazarbac{at}aub.edu.lb. The Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes through various mechanisms, including activation of the NF-B pathway. We found that cytoplasmic ubiquitylation of Tax C-terminal lysines is critical for Tax binding to the IB kinase complex and subsequent nuclear translocation of RelA. Conversely, we demonstrate that the same lysines are sumoylated in the nucleus, an event required for the formation of RelA/p300-enriched Tax nuclear bodies and full NF-B transcriptional activation. In contrast, Tax ubiquitylation and sumoylation are dispensable for its activation of CREB-dependent genes. Thus, ubiquitylation and sumoylation of the same residues of Tax regulate two essential steps controlling NF-B activation, demonstrating how these post-translational modifications can cooperate to promote Tax-induced transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Nejmeddine, V. S. Negi, S. Mukherjee, Y. Tanaka, K. Orth, G. P. Taylor, and C. R. M. Bangham HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse Blood, July 30, 2009; 114(5): 1016 - 1025. [Abstract] [Full Text] [PDF] S. Lambert, M. Bouttier, R. Vassy, M. Seigneuret, C. Petrow-Sadowski, S. Janvier, N. Heveker, F. W. Ruscetti, G. Perret, K. S. Jones, et al. HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165 Blood, May 21, 2009; 113(21): 5176 - 5185. [Abstract] [Full Text] [PDF] P. Yan, J. Fu, Z. Qu, S. Li, T. Tanaka, M. J. Grusby, and G. Xiao PDLIM2 suppresses human T-cell leukemia virus type I Tax-mediated tumorigenesis by targeting Tax into the nuclear matrix for proteasomal degradation Blood, April 30, 2009; 113(18): 4370 - 4380. [Abstract] [Full Text] [PDF] N. Shembade, N. S. Harhaj, M. Yamamoto, S. Akira, and E. W. Harhaj The Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Requires the Ubiquitin-Conjugating Enzyme Ubc13 for NF-{kappa}B Activation J. Virol., December 15, 2007; 81(24): 13735 - 13742. [Abstract] [Full Text] [PDF] T. Tsuji, N. Sheehy, V. W. Gautier, H. Hayakawa, H. Sawa, and W. W. Hall The Nuclear Import of the Human T Lymphotropic Virus Type I (HTLV-1) Tax Protein Is Carrier- and Energy-independent J. Biol. Chem., May 4, 2007; 282(18): 13875 - 13883. [Abstract] [Full Text] [PDF] N. S. Harhaj, S.-C. Sun, and E. W. Harhaj Activation of NF-{kappa}B by the Human T Cell Leukemia Virus Type I Tax Oncoprotein Is Associated with Ubiquitin-dependent Relocalization of I{kappa}B Kinase J. Biol. Chem., February 9, 2007; 282(6): 4185 - 4192. [Abstract] [Full Text] [PDF] S. S. Durkin, M. D. Ward, K. A. Fryrear, and O. J. Semmes Site-specific Phosphorylation Differentiates Active from Inactive Forms of the Human T-cell Leukemia Virus Type 1 Tax Oncoprotein J. Biol. Chem., October 20, 2006; 281(42): 31705 - 31712. [Abstract] [Full Text] [PDF] M. L. Gatza and S. J. Marriott Genotoxic Stress and Cellular Stress Alter the Subcellular Distribution of Human T-Cell Leukemia Virus Type 1 Tax through a CRM1-Dependent Mechanism. J. Virol., July 1, 2006; 80(13): 6657 - 6668. [Abstract] [Full Text] [PDF]

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