References of "Piette, Jacques"
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See detailVaricella-Zoster Virus IE4 Protein Interacts with SR Proteins and Exports mRNAs through the TAP/NXF1 Pathway.
Ote, Isabelle ULg; Vandevenne, Patricia ULg; Bontems, Sébastien ULg et al

in PLoS ONE (2009), 4(11), 7882

Available data suggest that the Varicella-Zoster virus (VZV) IE4 protein acts as an important regulator on VZV and cellular genes expression and could exert its functions at post-transcriptional level ... [more ▼]

Available data suggest that the Varicella-Zoster virus (VZV) IE4 protein acts as an important regulator on VZV and cellular genes expression and could exert its functions at post-transcriptional level. However, the molecular mechanisms supported by this protein are not yet fully characterized. In the present study, we have attempted to clarify this IE4-mediated gene regulation and identify some cellular partners of IE4. By yeast two-hybrid and immunoprecipitation analysis, we showed that IE4 interacts with three shuttling SR proteins, namely ASF/SF2, 9G8 and SRp20. We positioned the binding domain in the IE4 RbRc region and we showed that these interactions are not bridged by RNA. We demonstrated also that IE4 strongly interacts with the main SR protein kinase, SRPK1, and is phosphorylated in in vitro kinase assay on residue Ser-136 contained in the Rb domain. By Northwestern analysis, we showed that IE4 is able to bind RNA through its arginine-rich region and in immunoprecipitation experiments the presence of RNA stabilizes complexes containing IE4 and the cellular export factors TAP/NXF1 and Aly/REF since the interactions are RNase-sensitive. Finally, we determined that IE4 influences the export of reporter mRNAs and clearly showed, by TAP/NXF1 knockdown, that VZV infection requires the TAP/NXF1 export pathway to express some viral transcripts. We thus highlighted a new example of viral mRNA export factor and proposed a model of IE4-mediated viral mRNAs export. [less ▲]

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See detailRedox regulation of nuclear post-translational modifications during NF-kappaB activation.
Gloire, Geoffrey ULg; Piette, Jacques ULg

in Antioxidants & Redox Signaling (2009)

The transcription factor NF-kappaB controls the expression of hundreds of genes involved in the regulation of the immune/inflammatory response, development, and apoptosis. In resting cells, NF-kappaB ... [more ▼]

The transcription factor NF-kappaB controls the expression of hundreds of genes involved in the regulation of the immune/inflammatory response, development, and apoptosis. In resting cells, NF-kappaB proteins are sequestered in the cytoplasm through their tight association with IkappaB proteins. NF-kappaB activation relies on the signal-induced IkappaB phosphorylation and degradation, thereby allowing the nuclear translocation of NF-kappaB proteins. In the nucleus, several post-translational modifications of NF-kappaB and chromatin remodeling of target genes are mandatory for NF-kappaB DNA binding and full transcription. Since 1991, reactive oxygen species (ROS) have been implicated in NF-kappaB activation. ROS enhance the cytoplasmic signaling pathways leading to NF-kappaB nuclear translocation, but reduction/oxidation (redox) also controls several key steps in the nuclear phase of the NF-kappaB program, including chromatin remodeling, recruitment of co-activators, and DNA binding. Here we describe the redox regulation of NF-kappaB activity in the nucleus. [less ▲]

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See detailEffects of marginal iron overload on iron homeostasis and immune function in alveolar macrophages isolated from pregnant and normal rats.
Ward, Roberta J; Wilmet, Stephanie; Legssyer, Rachida et al

in Biometals (2009), 22(2), 211-23

The effects of changes in macrophage iron status, induced by single or multiple iron injections, iron depletion or pregnancy, on both immune function and mRNA expression of genes involved in iron influx ... [more ▼]

The effects of changes in macrophage iron status, induced by single or multiple iron injections, iron depletion or pregnancy, on both immune function and mRNA expression of genes involved in iron influx and egress have been evaluated. Macrophages isolated from iron deficient rats, or pregnant rats at day 21 of gestation, either supplemented with a single dose of iron dextran, 10 mg, at the commencement of pregnancy, or not, showed significant increases of macrophage ferroportin mRNA expression, which was paralleled by significant decreases in hepatic Hamp mRNA expression. IRP activity in macrophages was not significantly altered by iron status or the inducement of pregnancy +/- a single iron supplement. Macrophage immune function was significantly altered by iron supplementation and pregnancy. Iron supplementation, alone or combined with pregnancy, increased the activities of both NADPH oxidase and nuclear factor kappa B (NFkappaB). In contrast, the imposition of pregnancy reduced the ability of these parameters to respond to an inflammatory stimuli. Increasing iron status, if only marginally, will reduce the ability of macrophages to mount a sustained response to inflammation as well as altering iron homeostatic mechanisms. [less ▲]

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See detailNew asthma biomarkers: lessons from murine models of acute and chronic asthma.
Di Valentin, Emmanuel ULg; Crahay, Céline; Garbacki, Nancy ULg et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2009), 296(2), 185-97

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the ... [more ▼]

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma. [less ▲]

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See detailSynergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection
Reuse, sophie; Calao, Miriam; Kabeya, Kabamba et al

in PLoS ONE (2009), 4(6), 6093

The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus ... [more ▼]

The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer. In J-Lat cells, we showed that this synergism was due, at least partially, to the synergistic recruitment of unresponsive cells into the expressing cell population. A combination of prostratin+HDACI synergistically activated the 5' Long Terminal Repeat (5'LTR) from HIV-1 Major group subtypes representing the most prevalent viral genetic forms, as shown by transient transfection reporter assays. Mechanistically, HDACIs increased prostratin-induced DNA-binding activity of nuclear NF-kappaB and degradation of cytoplasmic NF-kappaB inhibitor, IkappaBalpha . Moreover, the combined treatment prostratin+HDACI caused a more pronounced nucleosomal remodeling in the U1 viral promoter region than the treatments with the compounds alone. This more pronounced remodeling correlated with a synergistic reactivation of HIV-1 transcription following the combined treatment prostratin+HDACI, as demonstrated by measuring recruitment of RNA polymerase II to the 5'LTR and both initiated and elongated transcripts. The physiological relevance of the prostratin+HDACI synergism was shown in CD8(+)-depleted peripheral blood mononuclear cells from HAART-treated patients with undetectable viral load. Moreover, this combined treatment reactivated viral replication in resting CD4(+) T cells isolated from similar patients. Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients. [less ▲]

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See detailMatrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?
Garbacki, Nancy ULg; Di Valentin, Emmanuel ULg; Piette, Jacques ULg et al

in Pulmonary Pharmacology & Therapeutics (2009), 22(4), 267-278

Among the large matrix metalloproteinases (MMPs) family, MMP-12, also referred to as macrophage elastase, plays a significant role in chronic pulmonary pathologies characterized by an intense tissue ... [more ▼]

Among the large matrix metalloproteinases (MMPs) family, MMP-12, also referred to as macrophage elastase, plays a significant role in chronic pulmonary pathologies characterized by an intense tissue remodeling such as asthma and COPD. This review will summarize knowledge about MMP-12 structure, functions and mechanisms of activation and regulation, including potential MMP-12 modulation by microRNA. As MMP-12 is involved in many tissue remodeling diseases, efforts have been made to develop specific synthetic inhibitors. However, at this time, very few chemical inhibitors have proved to be efficient and specific to a particular MMP. The relevance of silencing MMP-12 by RNA interference is highlighted. The specificity of this approach using siRNA or shRNA and the strategies to deliver these molecules in the lung are discussed. [less ▲]

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See detailThe proapoptotic C16-ceramide-dependent pathway requires the death-promoting factor Btf in colon adenocarcinoma cells.
Renert, Anne-Francoise; Leprince, Pierre ULg; Dieu, Marc et al

in Journal of Proteome Research (2009), 8(10), 4810-22

Ceramides are central molecules in sphingolipid metabolism. They are involved in the regulation of cancer-cell growth, differentiation, senescence and apoptosis. To better understand how these secondary ... [more ▼]

Ceramides are central molecules in sphingolipid metabolism. They are involved in the regulation of cancer-cell growth, differentiation, senescence and apoptosis. To better understand how these secondary messengers induce their biological effects, adenocarcinoma cells (HCT116) were treated with exogenous long-chain ceramides (C16-ceramide) in order to mimic endogenous sphingolipids. This treatment induced a decrease of cell viability partly due to apoptosis as shown by PARP cleavage and a decrease of pro-caspase 3. Two-dimensional differential in-gel electrophoresis (2D-DIGE) revealed the differential expression of 51 proteins in response to C16-ceramide. These proteins are notably involved in cell proliferation, apoptosis, protein transport and transcriptional regulation. Among them, the cell death-promoting factor Btf was found to be implicated in the apoptotic signal triggered by ceramide. In adenocarcinoma cells, Btf regulates apoptosis related proteins such as Mdm2, p53, BAX and pBcl-2 and thus plays an important role in the ceramide mediated cell death. These findings bring new insight into the proapoptotic ceramide-dependent signaling pathway. [less ▲]

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See detailActin-targeting natural compounds as tools to study the role of actin cytoskeleton in signal transduction.
Kustermans, Gaëlle ULg; Piette, Jacques ULg; Legrand, Sylvie ULg

in Biochemical Pharmacology (2008), 76(11)

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly ... [more ▼]

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly demonstrated that actin cytoskeleton can play a regulating role in several signalling pathways. Cells tightly regulate actin dynamics through numerous specific proteins in order to rapidly and locally respond to various stimuli. An obvious approach to determine the involvement of actin cytoskeleton in signalling pathways is the use of actin-targeting natural compounds. These drugs modulate actin dynamics, accelerating either polymerization or depolymerization, through various mechanisms. This review focus on the use of these actin-targeting drugs as tools to demonstrate the role of actin cytoskeleton in several signal transduction pathways such as those initiated from antigen receptor in T and B cells or those involving mitogen-activated protein kinases (MAPKs) or transcription factors NF-kB and SRF (serum response factor). In this last case (SRF), the use of various actin-targeting drugs participated in the elucidation of the molecular mechanism by which actin regulates SRF-mediated transcription. [less ▲]

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See detailMolecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells
Buytaert, E.; Matroule, J. Y.; Durinck, S. et al

in Oncogene (2008)

Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O(2), cytotoxic reactive oxygen species, which cause ... [more ▼]

Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O(2), cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38(MAPK) inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38(MAPK) inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer. [less ▲]

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See detailAre the IKKs and IKK-related kinases TBK1 and IKK-ε similarly activated ?
Chau, Tieu-Lan ULg; Gioia, Romain ULg; GATOT, Jean-Stéphane ULg et al

in Trends in Biochemical Sciences - Regular Edition (2008), 33

The IKKs, IKKa and IKKb, and the IKK-related kinases TBK1 and IKKe, play essential roles in innate immunity through signal-induced activation of NF-κB and IRF3/7, respectively. Although the signaling ... [more ▼]

The IKKs, IKKa and IKKb, and the IKK-related kinases TBK1 and IKKe, play essential roles in innate immunity through signal-induced activation of NF-κB and IRF3/7, respectively. Although the signaling events within these pathways have been extensively studied, the mechanisms of IKK and IKK-related complex assembly and activation remain poorly defined. Recent data provide insight into the requirement for scaffold proteins in complex assembly; NEMO coordinates some IKK complexes, whereas TANK, NAP1 or SINTBAD assemble TBK1 and IKKe complexes. The different scaffold proteins undergo similar post-translational modifications, including phosphorylation and non-degradative polyubiquitylation. Moreover, increasing evidence suggests that distinct scaffold proteins assemble IKK and potentially TBK1 and IKKε sub-complexes in a stimulus-specific manner, which might be a mechanism to achieve specificity. [less ▲]

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See detailGeldanamycin inhibits tyrosine phosphorylation-dependent NF-kB activation
Crèvecoeur, Julie ULg; Piette, Jacques ULg; Gloire, Geoffrey ULg

in Biochemical Pharmacology (2008), 75(11), 2183-2191

Hsp90 is a protein chaperone regulating the stability and activity of many signalling molecules. The requirement of Hsp90 activity in the NF-κB pathway has been recently reported by several authors using ... [more ▼]

Hsp90 is a protein chaperone regulating the stability and activity of many signalling molecules. The requirement of Hsp90 activity in the NF-κB pathway has been recently reported by several authors using the Hsp90 ATPase inhibitor Geldanamycin (GA), an anti-tumour drug. Hsp90 inhibition blocks the synthesis and activation of the IKK complex, the major kinases complex responsible for IκBα phosphorylation on serine 32 and 36, a key step for its degradation and the nuclear translocation of NF-κB. However, the effect of GA on other IκBα kinases, including tyrosine kinases, is unknown. In the present study, we investigated the effect of GA on NF-κB activation induced by sodium pervanadate (PV), a tyrosine phosphatase inhibitor triggering c-Src-mediated tyrosine phosphorylation of IκBα. We reporte for the first time that GA inhibits PV-induced IκBα tyrosine phosphorylation and degradation. Using an in vitro kinase assay, we demonstrated that GA inhibits the activity of c-Src as an IκBα tyrosine kinase, but not its cellular expression. As a result, GA blocked PV-induced NF-κB DNA binding activity on an exogenous κB element and on the endogenous iκbα promoter, thereby inhibiting IκBα transcription. Finally, we demonstrated that, despite NF-κB inhibition, pre-treatment with GA does not potentiate PV-induced apoptosis. We conclude that c-Src requires Hsp90 for its tyrosine kinase activity, and its inhibition by GA blocks c-Src-dependent signalling pathways, such as NF-κB activation induced by sodium pervanadate. The effect of GA on PV-induced apoptosis is discussed in the light of recent publications in the literature. [less ▲]

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See detailActin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells
Kustermans, Gaëlle ULg; El Mjiyad, Nadia ULg; Horion, Julie ULg et al

in Biochemical Pharmacology (2008), 76(10)

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation ... [more ▼]

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation and expression of pro-inflammatory genes. In the present study, we demonstrated that reorganization of actin cytoskeleton induced by Cytochalasin D (CytD), an actin-polymerization inhibitor, enhanced il-8 gene expression induced by TNFa and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional mechanisms were involved. CytD potentiated NF-kB-mediated transcription induced by both TNFa and LPS but via different mechanisms. In the case of LPS, the perturbation of actin dynamics increased the TLR4 levels at the cell membrane and consequently enhanced the IKK complex activation and NF-kB nuclear translocation. However, the canonical pathway involving the IKK complex and leading to the NF-kB translocation into the nucleus was not affected by actin remodelling in the case of TNFa. Interestingly, actin disruption primed p65 phosphorylation induced by TNFa and LPS, on Ser276 and Ser536, respectively, which suggested actin cytoskeleton could also modulate p65 transactivating activity. [less ▲]

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See detailRegulation of CD95/APO-1/Fas-induced apoptosis by protein phosphatases.
Gloire, Geoffrey ULg; Charlier, Edith ULg; Piette, Jacques ULg

in Biochemical Pharmacology (2008)

Triggering the CD95/APO-1/Fas receptor by CD95-L induces the assembly of the death-inducing signaling complex (DISC), which permits initiator caspases activation and progression of a signaling cascade ... [more ▼]

Triggering the CD95/APO-1/Fas receptor by CD95-L induces the assembly of the death-inducing signaling complex (DISC), which permits initiator caspases activation and progression of a signaling cascade that culminates in cellular apoptosis. Despite the CD95 receptor does not exhibit any kinase activity by itself, phosphorylation/dephosphorylation events seem important to regulate many aspects of CD95-mediated apoptosis. Here, we try to highlight particularly the importance of protein phosphatases in the modulation of the CD95 system. [less ▲]

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