Virus et cancer

Cadre général du travail

Le programme de recherche de notre groupe concerne l’oncoprotéine Tax du virus de la leucémie à cellules T de l’homme (HTLV-1), un rétrovirus dont l’infection est associée au développement d’une leucémie connue sous le nom de leucémie à cellules T de l’adulte (ATL). Plus spécifiquement, nous étudions les modifications post-traductionnelles (phosphorylation, ubiquitination, sumoylation, acétylation) de la protéine Tax et leurs conséquences sur sa localisation intracellulaire et ses activité transcriptionnelles (activation des voies de signalisation NF-kB et ATF/CREB) et transformantes (action sur les composantes qui contrôlent la progression du cycle cellulaire).

Équipe

• Françoise Bex
• Lodewick Julie
• Carla Sampaio

Publications

• Lodewick, J.; Lamsoul, I.; Bex, F. Move or Die: the Fate of the Tax Oncoprotein of HTLV-1. Viruses 2011, 3, 829-857.
• Avesani F, Romanelli MG, Turci M, Di Gennaro G, Sampaio C, Bidoia C, Bertazzoni U, Bex F. Association of HTLV Tax proteins with TAK1-binding protein 2 and RelA in calreticulin-containing cytoplasmic structures participates in Tax-mediated NF-κB activation.Virology. 2010 Dec 5;408(1):39-48. Epub 2010 Sep 27.PMID: 20875659
• Keutgens A, Zhang X, Shostak K, Robert I, Olivier S, Vanderplasschen A, Chapelle JP, Viatour P, Merville MP, Bex F, Gothot A, Chariot A. BCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1. J Biol Chem. 2010 Aug 13;285(33):25831-40. Epub 2010 Jun 17.PMID: 20558726
• Lodewick J, Lamsoul I, Polania A, Lebrun S, Burny A, Ratner L, Bex F. Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappaB pathway. Virology. 2009 Mar 30;386(1):68-78. PMID: 19200568.
• Turci M, Lodewick J, Righi P, Polania A, Romanelli MG, Bex F, Bertazzoni U. HTLV-2B Tax oncoprotein is modified by ubiquitination and sumoylation and displays intracellular localization similar to its homologue HTLV-1 Tax. Virology. 2009 Mar 30;386(1):6-11. PMID: 19195675.
• Terme JM, Wencker M, Favre-Bonvin A, Bex F, Gazzolo L, Duc Dodon M, Jalinot P. Cross talk between expression of the human T-cell leukemia virus type 1 Tax transactivator and the oncogenic bHLH transcription factor TAL1. J Virol. 2008 Aug;82(16):7913-22. PMID: 18495761.
• Mascaux C, Bex F, Martin B, Burny A, Haller A, Paesmans M, Willard-Gallo K, Ninane V, Sculier JP. The role of NPM, p14arf and MDM2 in precursors of bronchial squamous cell carcinoma. Eur Respir J. 2008 Sep;32(3):678-86. PMID: 18480108.
• Fiévez L, Desmet C, Henry E, Pajak B, Hegenbarth S, Garzé V, Bex F, Jaspar F, Boutet P, Gillet L, Vanderplasschen A, Knolle PA, Leo O, Moser M, Lekeux P, Bureau F. STAT5 is an ambivalent regulator of neutrophil homeostasis. PLoS ONE. 2007 Aug 15;2(1):e727. PMID: 17710127.
• Gloire G, Horion J, El Mjiyad N, Bex F, Chariot A, Dejardin E, Piette J. Promoter-dependent effect of IKKalpha on NF-kappaB/p65 DNA binding. J Biol Chem. 2007 Jul 20;282(29):21308-18. PMID: 17537731.
• Legrand-Poels S, Kustermans G, Bex F, Kremmer E, Kufer TA, Piette J. Modulation of Nod2-dependent NF-kappaB signaling by the actin cytoskeleton. J Cell Sci. 2007 Apr 1;120(Pt 7):1299-310. PMID: 17356065.
• Akl H, Badran BM, Zein NE, Bex F, Sotiriou C, Willard-Gallo KE, Burny A, Martiat P. HTLV-I infection of WE17/10 CD4+ cell line leads to progressive alteration of Ca2+ influx that eventually results in loss of CD7 expression and activation of an antiapoptotic pathway involving AKT and BAD which paves the way for malignant transformation. Leukemia. 2007 Apr;21(4):788-96. PMID: 17287851.
• Brulet JM, Maudoux F, Thomas S, Thielemans K, Burny A, Leo O, Bex F, Hallez S. DNA vaccine encoding endosome-targeted human papillomavirus type 16 E7 protein generates CD4+ T cell-dependent protection. Eur J Immunol. 2007 Feb;37(2):376-84. PMID: 17274002.
• Baydoun H, Duc-Dodon M, Lebrun S, Gazzolo L, Bex F. Regulation of the human T-cell leukemia virus gene expression depends on the localization of regulatory proteins Tax, Rex and p30II in specific nuclear subdomains. Gene. 2007 Jan 15;386(1-2):191-201. PMID: 17071021.
• Cardoso F, Durbecq V, Laes JF, Badran B, Lagneaux L, Bex F, Desmedt C, Willard-Gallo K, Ross JS, Burny A, Piccart M, Sotiriou C. Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner. Mol Cancer Ther. 2006 Dec;5(12):3042-51. PMID: 17148762.
• Lamsoul I, Lodewick J, Lebrun S, Brasseur R, Burny A, Gaynor RB, Bex F. Exclusive ubiquitination and sumoylation on overlapping lysine residues mediate NF-kappaB activation by the human T-cell leukemia virus tax oncoprotein. Mol Cell Biol. 2005 Dec;25(23):10391-406. PMID: 1628785.
• Chiari E., Lamsoul I., Lodewick J., Chopin C., Bex F., and Pique C. 2004 Stable ubiquitination of human T-cell leukemia virus type 1 tax is required for proteasome binding. J. Virol. 78, 11823-11832.

Collaborations

• Institut de Recherche Interdisciplinaire (IRIBHM), ULB (P. Roger)
• Department of Mother and Child, Section of Biology and Genetics, Université de Vérone, Italie (U. Bertazzoni et MG Romanelli)
• Virologie Humaine, INSERM-U412, Ecole Normale Supérieure, Lyon, France (M. Duc-Dodon)
• Université de Liège - Facultés universitaires des Sciences Agronomiques de Gembloux (L. Willems)

Plusieurs collaborations sont centrées sur l’utilisation d’un microscope confocal équipé de 3 lasers dans divers domaines de recherche.

• Department of Intensive Care and Thorasic Oncology, Institut Jules Bordet, ULB (J-P Sculier)
• Laboratory of Experimental Hematology, Institut Jules Bordet, ULB (P. Martiat)
• Virology-Immunology, GIGA Research, ULG (J. Piette)
• Translation Research Unit, Center for Education and Research in Food and Chemical Industry, Institut Jules Bordet, ULB (C. Sotiriou)
• Laboratory of Cellular and Molecular Physiology, GIGA Research, ULG (F. Bureau)
• Laboratory of Chemical Biology, IBMM, ULB (S. Hallez)