Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome
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- Youmna Kfoury
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon;
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- Niclas Setterblad
- Imagery Department of the Institut Universitaire d'Hématologie Institut Fédératif de Recherche 105, Paris, France;
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- Marwan El-Sabban
- Department of Human Morphology, American University of Beirut, Beirut, Lebanon;
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- Alessia Zamborlini
- Unité Mixte de Recherche (UMR) 7212 Centre National de la Recherche Scientifique (CNRS), U944 Inserm, Laboratoire Associé au Comité de Paris de la Ligue contre le Cancer, Paris, France;
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- Zeina Dassouki
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon;
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- Hiba El Hajj
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon;
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- Olivier Hermine
- CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France;
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- Claudine Pique
- Inserm U1016, CNRS UMR 8104, Université Paris Descartes, Institut Cochin, Department of Cell Biology and Host-Pathogens Interactions, Paris, France; and
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- Hugues de Thé
- Unité Mixte de Recherche (UMR) 7212 Centre National de la Recherche Scientifique (CNRS), U944 Inserm, Laboratoire Associé au Comité de Paris de la Ligue contre le Cancer, Paris, France;
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- Ali Saïb
- Unité Mixte de Recherche (UMR) 7212 Centre National de la Recherche Scientifique (CNRS), U944 Inserm, Laboratoire Associé au Comité de Paris de la Ligue contre le Cancer, Paris, France;
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- Ali Bazarbachi
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon;
書誌事項
- 公開日
- 2011-01-06
- DOI
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- 10.1182/blood-2010-05-285742
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>The human T-lymphotropic virus type I oncoprotein Tax is critical for T-cell transformation, acting mainly through nuclear factor kappa B essential modulator (NEMO) binding and subsequent nuclear factor-κB activation. Tax localizes to Tax nuclear bodies and to the centrosome and is subjected to ubiquitylation and small ubiquitin-like modifier (SUMO)ylation, which are both necessary for complete transcriptional activation. Using the photoconvertible fluorophore Dendra-2 coupled with live video confocal microscopy, we show for the first time that the same Tax molecule shuttles among Tax nuclear bodies and between these nuclear bodies and the centrosome, depending on its posttranslational modifications. Ubiquitylation targets Tax to nuclear bodies to which NEMO is recruited and subsequently SUMOylated. We also demonstrate that Tax nuclear bodies contain the SUMOylation machinery including SUMO and the SUMO conjugating enzyme Ubc9, strongly suggesting that these nuclear bodies represent sites of active SUMOylation. Finally, both ubiquitylation and SUMOylation of Tax control NEMO targeting to the centrosome. Altogether, we are proposing a model where both ubiquitylation and SUMOylation of Tax control the shuttling of Tax and NEMO between the cytoplasmic and nuclear compartments.</jats:p>
収録刊行物
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- Blood
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Blood 117 (1), 190-199, 2011-01-06
American Society of Hematology