References of "Dewulf, Jean-Francois"
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See detailInhibition of Tax transformation activity using a small molecule targetting Tax/PDZ domain interactions.
Blibek, Karim ULg; Fujii, Naoaki; Legros, Sebastien et al

Poster (2013, June 29)

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL) and tropical spastic ... [more ▼]

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP), an immune degenerative neurologic syndrome. All the four viruses share a similar genomic organization and encode transforming Tax oncoproteins. In contrast to HTLV-2 and 4, HTLV-1 and 3 Tax proteins contain a PSD-95/Drosophila Discs Large/Zona Occludens-I (PDZ) binding motif at their C-terminal that has been shown to play crucial roles in the distinct transforming properties of the Tax proteins. To systematically investigate PDZ-containing proteins roles in HTLV-1 biology, we initiated a global interactome network analysis of Tax and associated human PDZ-containing proteins. This was accomplished through the use of our framework of binary interactome mapping that includes stringent yeast two hybrid and pulldown screening, systematic retesting by protein complementation assay and evaluation of PDZ gene expression in T lymphocytes. [less ▲]

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See detailInhibition of Tax transformation activity using a small molecule targetting Tax/PDZ domain interactions.
Blibek, Karim ULg; Fujii, Naoki; Legros, Sebastien et al

Poster (2013, June 29)

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL). All the four viruses ... [more ▼]

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL). All the four viruses share a similar genomic organization and encode transforming Tax oncoproteins. In contrast to HTLV-2 and 4, HTLV-1 and 3 Tax proteins contain a PSD-95/Drosophila Discs Large/Zona Occludens-I (PDZ) binding motif at their C-terminal that has been shown to play crucial roles in the distinct transforming properties of the Tax proteins. Here, we used a collection of human full-length protein-coding open reading frames (ORFeome v3.1) to identify novel PDZ domain containing proteins that specifically interact with HTLV-1 Tax. Novel Tax interactors include syntenin-1 and -2, LNX2, DVL3, GIPC2, INTU, PDLIM4 and -7, RADIL and RGS3. These proteins are involved in diverse biological processes including cell division, cell fate determination and cell suvival. We further characterized interaction between Tax and syntenins and showed that, FJ9 a small molecule able to disrupt Tax/PDZ interactions, could antagonize Tax-transformation activity in rat-1 model. Our study identify novel PDZ-containg proteins interacting with HTLV-1 Tax and provides the first example where Tax protein-protein interactions whith PDZ-containing proteins and Tax-transformation capacity could be inhibited by a small molecule. [less ▲]

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See detailDisruption of PDZ protein-protein interactions inhibits Tax transformation and HTLV-1 infection capacities.
Twizere, Jean-Claude ULg; DEWULF, Jean-François; Blibek, Karim ULg et al

Poster (2011, June 06)

Human T-cell leukemia virus type I (HTLV-1) encodes a Tax oncoprotein that is critical for both viral replication and cellular transformation. HTLV-1 Tax possesses a PDZ domain binding motif (PBM) at its ... [more ▼]

Human T-cell leukemia virus type I (HTLV-1) encodes a Tax oncoprotein that is critical for both viral replication and cellular transformation. HTLV-1 Tax possesses a PDZ domain binding motif (PBM) at its C-terminus that is essential for its transforming activity in a Rat-1 model and for IL-2. Tax has been shown to interact with several PDZ domain containing proteins including PSD-95, Beta1-syntrophin, the precursor of interleukin-16, the mammalian homolog of the Drosophila discs large tumor suppressor protein Dlg, PDLIM2, Lin7, hTid1, Tip1, hScrib and MAGI3. In the 15th International Conference on Human Retrovirology: HTLV and Related Retroviruses, we will present a specificity map for the Tax/PDZ domain interactions generated using the human ORFeome 5.1. and we will focus on some of the new Tax/PDZ interactions. [less ▲]

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See detailThe HTLV-1 Tax interactome.
Boxus, Mathieu ULg; Twizere, Jean-Claude ULg; Legros, Sebastien et al

in Retrovirology (2008), 5

The Tax1 oncoprotein encoded by Human T-lymphotropic virus type I is a major determinant of viral persistence and pathogenesis. Tax1 affects a wide variety of cellular signalling pathways leading to ... [more ▼]

The Tax1 oncoprotein encoded by Human T-lymphotropic virus type I is a major determinant of viral persistence and pathogenesis. Tax1 affects a wide variety of cellular signalling pathways leading to transcriptional activation, proliferation and ultimately transformation. To carry out these functions, Tax1 interacts with and modulates activity of a number of cellular proteins. In this review, we summarize the present knowledge of the Tax1 interactome and propose a rationale for the broad range of cellular proteins identified so far. [less ▲]

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See detailHuman T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling.
Twizere, Jean-Claude ULg; Springael, Jean-Yves; Boxus, Mathieu ULg et al

in Blood (2007), 109(3), 1051-60

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 ... [more ▼]

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. [less ▲]

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