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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 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 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 Nasr, R. Articles by Bazarbachi, A. Search for Related Content PubMed PubMed Citation Articles by Nasr, R. Articles by Bazarbachi, A. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Thé, Claudine Pique, and Ali Bazarbachi From the Department of Internal Medicine and the Department of Human Morphology, American University of Beirut, Lebanon; Unité Mixté de Recherche (UMR) 7151 Centre National de la Recherche Scientifique (CNRS)/University of Paris 7; Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes (EPVO), Institut Pasteur, Paris, France; and CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France. The Tax oncoprotein plays a crucial role in the proliferation and transformation of human T-cell leukemia virus type I (HTLV-I)–infected T lymphocytes through various mechanisms, including activation of the nuclear factor (NF)–B pathway. We found that cytoplasmic ubiquitylation of Tax C-terminal lysines is critical for Tax binding to the IkappaB 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 cyclic adenosine monophosphate response element binding protein (CREB)–dependent genes. Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-B activation, demonstrating how these posttranslational 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: 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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