Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling.
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.
Twizere
Jean-Claude
JC
Department of Cellular and Molecular Biology, Faculty of Gembloux, Belgium. twizere.jc@fsagx.ac.be
Springael
Jean-Yves
JY
Boxus
Mathieu
M
Burny
Arsène
A
Dequiedt
Franck
F
Dewulf
Jean-François
JF
Duchateau
Julie
J
Portetelle
Daniel
D
Urbain
Patrice
P
Van Lint
Carine
C
Green
Patrick L
PL
Mahieux
Renaud
R
Parmentier
Marc
M
Willems
Luc
L
Kettmann
Richard
R
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
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