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See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Barez, Pierre-Yves ULg; Willems, Luc ULg

Poster (2012, June 22)

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most important are the adult T ... [more ▼]

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most important are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). We are interested in the mechanisms of transformation by the viral Tax oncoprotein. Recently, we showed that Tax interacts with the minichromosome maintenance MCM2-7 helicase and binds to origins of DNA replication (Boxus et al, 2012 Blood 119:151). Thereby, Tax modulates the spatiotemporal program of origin activation during the S phase of cell cycle. In fact, Tax accelerates S phase progression by inducing early firing of late replication origins. Concomitantly, Tax-MCM2-7 interplay also modulates viral transcription. Together, our data demonstrates that interaction between Tax and MCM2-7 is involved in replication reprogramming and viral transcription. [less ▲]

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See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Boxus, Mathieu ULg; Twizere, Jean-Claude ULg; Legros, Sébastien et al

in Blood (2012), 119

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes ... [more ▼]

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes, expand through mitotic division and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains advancing their replication timing in early S phase. [less ▲]

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See detailInteraction of HTLV-­1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Willems, Luc ULg

Conference (2013, January 28)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

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See detailInteraction of hydroxylamine with the S1, S2 and S3 states of the water-oxidizing complex in etiochloroplasts of oat
Franck, Fabrice ULg; Schmid, G. H.

in Biochimica et Biophysica Acta (1989), 977

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See detailInteraction of lipopeptides from Bacillus subtilis with lipid vesicles
Deleu, Magali ULg; Paquot, Michel ULg; Olofsson, Gerd et al

Poster (2004)

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See detailInteraction of nanoparticles for drug delivery with biomimetic model membranes
Frost, Rickard; Cerda, Bernadino; Grandfils, Christian ULg et al

Poster (2009)

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See detailThe interaction of nanoparticles for drug delivery with biomimetic model membranes
Frost, Rickard; Cerda, Bernadino; Grandfils, Christian ULg et al

Poster (2009, February 24)

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See detailInteraction of odorous lactones with phospholipids: Implications in toxicity towards producing yeast cells
Aguedo, Mario ULg; Beney, L.; Waché, Y. et al

in Biotechnology Letters (2002), 24(23), 1975-1979

Some lactonic aroma compounds, that can be produced industrially by microorganisms, become toxic towards the producing cells as these compounds reach high concentrations in the culture medium. To ... [more ▼]

Some lactonic aroma compounds, that can be produced industrially by microorganisms, become toxic towards the producing cells as these compounds reach high concentrations in the culture medium. To determine the manner by which these metabolites may influence yeast physiology, the effects of four lactones (concentration range of 100 to 300 mg l-1) on the growth of Yarrowia lipolytica and on the phase behaviour of deuterated dimyristoylphos-phatidylcholine (DMPC-d27) were studied. The results showed that the hydrophobic lactones decrease the phase transition temperature (Tm) of DMPC-d27 bilayers and that Tm decrease (ΔTm) was related to the inhibitory action of the lactones on yeast growth (evaluated by the lag time). These results suggest that whatever the lactone, a ΔTm of at least 2.5°C resulted in a total growth inhibition: this implicates the lactone-phospholipids interaction in the mechanism of yeast growth inhibition. The test used in the present study may be a predicting method to assess the in vivo action of potential membrane active compounds. [less ▲]

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See detailInteraction of retroviral Tax oncoproteins with tristetraprolin and regulation of tumor necrosis factor-alpha expression.
Twizere, Jean-Claude ULg; Kruys, Veronique; Lefebvre, Laurent et al

in Journal of the National Cancer Institute (2003), 95(24), 1846-59

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell ... [more ▼]

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell leukemia viruses and bovine leukemia virus). To better understand the molecular pathways leading to cell transformation, we aimed to identify cellular proteins interacting with Tax. METHODS: We used a yeast two-hybrid system to identify interacting cellular proteins. Interactions between Tax and candidate interacting cellular proteins were confirmed by glutathione S-transferase (GST) pulldown assays, co-immunoprecipitation, and confocal microscopy. Functional interactions between Tax and one interacting protein, tristetraprolin (TTP), were assessed by analyzing the expression of tumor necrosis factor-alpha (TNF-alpha), which is regulated by TTP, in mammalian cells (HeLa, D17, HEK 293, and RAW 264.7) transiently transfected with combinations of intact and mutant Tax and TTP. RESULTS: We obtained seven interacting cellular proteins, of which one, TTP, was further characterized. Tax and TTP were found to interact specifically through their respective carboxyl-terminal domains. The proteins colocalized in the cytoplasm in a region surrounding the nucleus of HeLa cells. Furthermore, coexpression of Tax was associated with nuclear accumulation of TTP. TTP is an immediate-early protein that inhibits expression of TNF-alpha at the post-transcriptional level. Expression of Tax reverted this inhibition, both in transient transfection experiments and in stably transfected macrophage cell lines. CONCLUSION: Tax, through its interactions with the TTP repressor, indirectly increases TNF-alpha expression. This observation is of importance for the cell transformation process induced by leukemogenic retroviruses, because TNF-alpha overexpression plays a central role in pathogenesis. [less ▲]

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See detailInteraction Of Surfactin With Membranes: A Computational Approach
Deleu, Magali ULg; Bouffioux, O.; Razafindralambo, Hary ULg et al

in Langmuir (2003), 19(8),

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See detailInteraction of the 106-126 prion peptide with lipid membranes and potential implication for neurotoxicity.
Dupiereux-Fettweis, Ingrid ULg; Zorzi, Willy ULg; Lins, Laurence ULg et al

in Biochemical and Biophysical Research Communications (2005), 331(4), 894-901

Prion diseases are fatal neurodegenerative disorders characterized by the accumulation in the brain of an abnormally misfolded, protease-resistant, and beta-sheet rich pathogenic isoform (PrP(SC)) of the ... [more ▼]

Prion diseases are fatal neurodegenerative disorders characterized by the accumulation in the brain of an abnormally misfolded, protease-resistant, and beta-sheet rich pathogenic isoform (PrP(SC)) of the cellular prion protein (PrP(C)). In the present work, we were interested to study the mode of prion protein interaction with the membrane using the 106-126 peptide and small unilamellar lipid vesicles as model. As previously demonstrated, we showed by MTS assay that PrP 106-126 induces alterations in the human neuroblastoma SH-SY5Y cell line. We demonstrated for the first time by lipid-mixing assay and by the liposome vesicle leakage test that PrP 106-126, a non-tilted peptide, induces liposome fusion thus a potential cell membrane destabilization, as supported by membrane integrity assay (LDH). By circular dichroism (CD) analysis we showed that the fusogenic property of PrP 106-126 in the presence of liposome is associated with a predominantly beta-sheet structure. These data suggest that the fusogenic property associated with a predominant beta-sheet structure exhibited by the prion peptides contributes to the neurotoxicity of these peptides by destabilizing cellular membranes. The latter might be attached at the membrane surface in a parallel orientation as shown by molecular modeling. [less ▲]

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See detailInteraction Of The Macrolide Azithromycin With Phospholipids .2. Biophysical And Computer-Aided Conformational Studies
Montenez, Jp.; Vanbambeke, F.; Piret, J. et al

in European Journal of Pharmacology (1996), 314(1-2), 215-27

In a comparison paper, we show the azithromycin causes a lysosomal phospholipidosis in cultured cells, binds in vitro to negatively charged bilayers without causing aggregation or fusion, and inhibits ... [more ▼]

In a comparison paper, we show the azithromycin causes a lysosomal phospholipidosis in cultured cells, binds in vitro to negatively charged bilayers without causing aggregation or fusion, and inhibits lysosomal phospholipase A1. In this paper, we show that azithromycin decreases the mobility of the phospholipids in negatively charged liposomes (using 31P nuclear magnetic resonance) and that it increases the fluidity of the acyl chains close to the hydrophilic/hydrophobic interface, but not deeper into the hydrophobic domain (assessed by measuring the fluorescence polarization of trimethylammonium-diphenylhexatriene and diphenyhexatriene, respectively). Computer-aided conformational analysis of mixed monolayers of azithromycin and phosphatidylinositol shows that the drug can be positioned largely in the hydrophobic domain, but close to the interface, with the macrocycle facing the C1 of the fatty acids (allowing the N9a endocyclic tertiary amine to interact with the phospho-groups), the cladinose located on the hydrophobic side of the lipid/water interface and the desosamine projected into the hydrophobic domain. This position is consistent with the experimental data. Analysis of virtual molecules shows that this unanticipated behavior to the shielding of the ionizable N3' amino-group in the desosamine by methyl-groups, and to the wide dispersion of hydrophobic domains all over the molecule. The interaction of azithromycin with phospholipids may account for some of its unusual pharmacokinetic properties and for its potential to cause lysosomal phospholipidosis. [less ▲]

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See detailInteraction-free Generation of Angular Momentum Eigenstates in Remote Qubits
Thiel, C.; Maser, A.; Bastin, Thierry ULg et al

Poster (2008)

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See detailInteractions at large distances and spin effects in nucleon-nucleon and nucleon-nuclei scattering
Cudell, Jean-René ULg; Predazzi, E.; Selyugin, Oleg Viktorovich

in Physics of Particles and Nuclei (2004), 35(Suppl. 1), 75-78

The momentum transfer dependence of the slopes of the spin-non-flip and spin-flip amplitudes is analyzed. It is shown that the long tail of the hadronic potential in impact parameter space leads, for ... [more ▼]

The momentum transfer dependence of the slopes of the spin-non-flip and spin-flip amplitudes is analyzed. It is shown that the long tail of the hadronic potential in impact parameter space leads, for hadron-hadron interactions, to a larger value of the slope for the reduced spin-flip amplitude than for the spin-non-flip amplitude. It is also shown that the preliminary measurement of A(N) obtained by the E950 Collaboration confirms such behavior of the hadron spin-flip amplitude. [less ▲]

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See detailInteractions between acetylcholine and substance P effects on lung mechanics in the rabbit.
Delaunois, Annie ULg; Gustin, Pascal ULg; Segura, P. et al

in Fundamental & Clinical Pharmacology (1996), 10(3), 278-88

The pharmacological mechanisms involved in the acetylcholine (ACh)- and substance P (SP)-induced changes in pulmonary mechanics were studied in isolated perfused rabbit lungs. Tracheal pressure (Ptr) and ... [more ▼]

The pharmacological mechanisms involved in the acetylcholine (ACh)- and substance P (SP)-induced changes in pulmonary mechanics were studied in isolated perfused rabbit lungs. Tracheal pressure (Ptr) and airflow were measured by a Fleisch pneumotachograph and pressure transducers. Air volume, lung resistance (RL) and dynamic compliance (Cdyn) were calculated. ACh induced a dose-dependent increase in Ptr and RL, and a decrease in Cdyn. These effects were strongly prevented by atropine, and partly by SR140333, a neurokinin NK1 receptor antagonist; SR48968, a neurokinin NK2 receptor antagonist; indomethacin and antihistaminics. Ketanserin had no significant protective effect against ACh. SP also induced concentration-dependent increases in RL and decreases in Cdyn. SR140333 and atropine strongly inhibited the effects of SP, while ketanserin, SR48968, antihistaminics and indomethacin did not protect the lungs against this drug. 5-hydroxytryptamine induced no significant change in lung mechanic parameters. Cumulative concentrations of histamine increased RL and decreased Cdyn. We conclude that ACh-induced changes in lung resistance and compliance are in part mediated by a direct effect on airway smooth muscle and in part by the stimulation of C fibers, by the release of histamine from mast cells and by the synthesis of arachidonic acid metabolites. In turn, the effects of SP on lung mechanics are partly due to cholinergic activation. [less ▲]

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See detailInteractions between Active-Site Serine Beta-Lactamases and So-Called Beta-Lactamase-Stable Antibiotics. Kinetic and Molecular Modelling Studies
Matagne, André ULg; Lamotte-Brasseur, J.; Frère, Jean-Marie ULg

in European Journal of Biochemistry (1993), 217(1), 61-67

The interactions between imipenem and four monobactams and three class A beta-lactamases have been studied in detail. Despite their reputation as being beta-lactamase-stable, some of these compounds were ... [more ▼]

The interactions between imipenem and four monobactams and three class A beta-lactamases have been studied in detail. Despite their reputation as being beta-lactamase-stable, some of these compounds were significantly hydrolysed by the enzymes. The results obtained with the Streptomyces albus G beta-lactamase have been analysed in the light of molecular modelling studies. The discussion is extended to include other so-called beta-lactamase-stable antibiotics to demonstrate that this appellation can often be misleading. [less ▲]

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See detailInteractions between Active-Site-Serine Beta-Lactamases and Compounds Bearing a Methoxy Side Chain on the Alpha-Face of the Beta-Lactam Ring: Kinetic and Molecular Modelling Studies
Matagne, André ULg; Lamotte-Brasseur, J.; Dive, Georges ULg et al

in Biochemical Journal (1993), 293((Pt 3)), 607-611

The interactions between three class A beta-lactamases and compounds bearing a methoxy side chain on the alpha-face of the beta-lactam ring (cefoxitin, moxalactam and temocillin) have been studied. When ... [more ▼]

The interactions between three class A beta-lactamases and compounds bearing a methoxy side chain on the alpha-face of the beta-lactam ring (cefoxitin, moxalactam and temocillin) have been studied. When compared with the situation prevailing with good substrates, both acylation and deacylation steps appeared to be severely impaired. Molecular modelling studies of the structures of the Henri-Michaelis complexes and of the acyl-enzymes indicate a major displacement of the crystallographically observed water molecule which connects the glutamate-166 and serine-70 side chains and underline the role of this water molecule in both reaction steps. [less ▲]

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