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Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling

par Twizere, Jean-Claude;Springael, Jean-Yves ;Boxus, Mathieu;Burny, Arsène ;Dequiedt, Franck;Dewulf, Jean-François;Duchateau, Julie;Portetelle, Daniel ;Urbain, Patrice;Van Lint, Carine ;Green, Patrick L.;Mahieux, Renaud;Parmentier, Marc ;Willems, Lucas ;Kettmann, Richard
Référence Blood, 109, 3, page (1051-1060)
Publication Publié, 2007

Article révisé par les pairs

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Résumé :

Human T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and neurological syndromes. HTLV-1 encodes the oncoprotein Tax-1, which modulates viral and cellular gene expression leading to T-cell transformation. Guanine nucleotide-binding proteins (G proteins) and G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins known and are involved in the regulation of most biological functions. Here, we report an interaction between HTLV-1 Tax oncoprotein and the G-protein β subunit. Interestingly, though the G-protein β subunit inhibits Tax-mediated viral transcription, Tax-1 perturbs G-protein β subcellular localization. Functional evidence for these observations was obtained using conditional Tax-1-expressing transformed T-lymphocytes, where Tax expression correlated with activation of the SDF-1/CXCR4 axis. Our data indicated that HTLV-1 developed a strategy based on the activation of the SDF-1/CXCR4 axis in the infected cell; this could have tremendous implications for new therapeutic strategies. © 2007 by The American Society of Hematology.