title: Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling.
abstract: 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 beta subunit. Interestingly, though the G-protein beta subunit inhibits Tax-mediated viral transcription, Tax-1 perturbs G-protein beta 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.
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Gembloux, Belgium. twizere.jc@fsagx.ac.be
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Twizere
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Springael
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boxus
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.forename: Franck
authors.initials: F
authors.lastname: Dequiedt
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dewulf
authors.forename: Julie
authors.initials: J
authors.lastname: Duchateau
authors.forename: Daniel
authors.initials: D
authors.lastname: Portetelle
authors.forename: Patrice
authors.initials: P
authors.lastname: Urbain
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Green
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
authors.forename: Marc
authors.initials: M
authors.lastname: Parmentier
authors.forename: Luc
authors.initials: L
authors.lastname: Willems
authors.forename: Richard
authors.initials: R
authors.lastname: Kettmann
mesh_terms: D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D006800:Deltaretrovirus Infections; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes; D014161:Transduction, Genetic
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016356:Gene Products, tax; D019718:Receptors, CXCR4; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins