References of "Piette, Jacques"
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See detailThe role of SHIP1 in T-lymphocyte life and death
Gloire, Geoffrey ULg; Erneux, Christophe; Piette, Jacques ULg

in Biochemical Society Transactions (2007), 35(Pt 2), 277-280

SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1], an inositol 5-phosphatase expressed in haemopoietic cells, acts by hydrolysing the 5-phosphates from PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4 ... [more ▼]

SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1], an inositol 5-phosphatase expressed in haemopoietic cells, acts by hydrolysing the 5-phosphates from PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4), thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathway. SHIP1 plays a major role in inhibiting proliferation of myeloid cells. As a result, SHIP1(-/-) mice have an increased number of neutrophils and monocytes/macrophages due to enhanced survival and proliferation of their progenitors. Although SHIP1 contributes to PtdIns(3,4,5)P(3) metabolism in T-lymphocytes, its exact role in this cell type is much less explored. Jurkat cells have recently emerged as an interesting tool to study SHIP1 function in T-cells because they do not express SHIP1 at the protein level, thereby allowing reintroduction experiments in a relatively easy-to-use system. Data obtained from SHIP1 reintroduction have revealed that SHIP1 not only acts as a negative player in T-cell lines proliferation, but also regulates critical pathways, such as NF-kappaB (nuclear factor kappaB) activation, and also appears to remarkably inhibit T-cell apoptosis. On the other hand, experiments using primary T-cells from SHIP1(-/-) mice have highlighted a new role for SHIP1 in regulatory T-cell development, but also emphasize that this protein is not required for T-cell proliferation. In support of these results, SHIP1(-/-) mice are lymphopenic, suggesting that SHIP1 function in T-cells differs from its role in the myeloid lineage. [less ▲]

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See detailCaractérisation de la protéine 9p du virus de la varicelle et du zona (VZV)
Joris-Gerards, Aline; BONTEMS, Sébastien ULg; Di Valentin et al

Poster (2007)

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See detailHIV-1 protease inhibitors do not interfere with provirus transcription and host cell apoptosis induced by combined treatment TNF-alpha plus TSA
Vandergeeten, Claire ULg; Quivy, Vincent; Moutschen, Michel ULg et al

in Biochemical Pharmacology (2007), 73(11), 1738-1748

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to ... [more ▼]

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to eliminate the latently infected cellular reservoirs by forcing gene expression in presence of HAART to prevent spreading of the infection by the newly synthesized viruses. Many studies have reported that a combination of a histone deacetylase inhibitor (HDACi) (i.e. TSA, NaBut, Valproic acid,...) with a pro-inflammatory cytokine (i.e. TNF alpha, IL-1,...) reactivates in a synergistic manner HIV-1 transcription in latently infected cells. The aim of the present study was to determine whether HIV-1 protease inhibitors (PIs) used in HAART (such as Saquinavir, Indinavir, Nelfinavir, Lopinavir, Ritonavir and Amprenavir) could interfere with the potential purge of the cellular reservoirs induced by a combined treatment involving TSA and TNF alpha. We showed, in two HIV-1 latently infected cell lines (ACH-2 and U1) that all PIs efficiently inhibited release of mature viral particles but did neither affect cell apoptosis nor NF-kappa B induction and HIV-1 transcription activation following combined treatment with TNF alpha + TSA. This study is encouraging in the fight against HIV-1 and shows that PIs should be compatible with an inductive adjuvent therapy for latent reservoir reduction/elimination in association with efficient HAART regimens. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailHistone deacetylase inhibitor trichostatin A sustains sodium pervanadate-induced NF-kappa B activation by delaying IkappaBalpha mRNA resynthesis : comparison with tumor necrosis factor alpha
Horion, Julie ULg; Gloire, Geoffrey ULg; El Mjiyad, Nadia et al

in Journal of Biological Chemistry (2007), 282(21), 15383

NF-kappaB is a crucial transcription factor tightly regulated by protein interactions and post-translational modifications, like phosphorylation and acetylation. A previous study has shown that ... [more ▼]

NF-kappaB is a crucial transcription factor tightly regulated by protein interactions and post-translational modifications, like phosphorylation and acetylation. A previous study has shown that trichostatin A (TSA), a histone deacetylase inhibitor, potentiates tumor necrosis factor (TNF) alpha-elicited NF-kappaB activation and delays IkappaBalpha cytoplasmic reappearance. Here, we demonstrated that TSA also prolongs NF-kappaB activation when induced by the insulino-mimetic pervanadate (PV), a tyrosine phosphatase inhibitor that initiates an atypical NF-kappaB signaling. This extension is similarly correlated with delayed IkappaBalpha cytoplasmic reappearance. However, whereas TSA causes a prolonged IKK activity when addedtoTNFalpha, it does notwhenaddedtoPV.Instead, quantitative reverse transcriptase-PCR revealed a decrease of ikappabalphamRNAlevel after TSA addition to PV stimulation. This synthesis deficit of the inhibitor could explain the sustained NF-kappaB residence in the nucleus. In vivo analysis by chromatin immunoprecipitation assays uncovered that, forPVinduction but not forTNFalpha, the presence of TSA provokes several impairments on the ikappabalphapromoter: (i) diminution of RNA Pol II recruitment; (ii) reduced acetylation and phosphorylation of histone H3-Lys14 and -Ser10, respectively; (iii) decreased presence of phosphorylated p65-Ser536; and (iv) reduction of IKKalphabinding. The recruitment of these proteins on the icam-1 promoter, another NF-kappaB-regulated gene, is not equally affected, suggesting a promoter specificity of PV with TSA stimulation. Taken together, these data suggest that TSA acts differently depending on the NF-kappaB pathway and the targeted promoter in question. This indicates that one overall histone deacetylase role is to inhibit NF-kappaB activation by molecular mechanisms specific of the stimulus and the promoter. [less ▲]

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See detailVaricella-zoster virus modulates NF-kappaB recruitment on selected cellular promoters.
El Mjiyad, Nadia ULg; Bontems, Sébastien ULg; Gloire, Geoffrey ULg et al

in Journal of Virology (2007), 81(23), 13092-104

Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor ... [more ▼]

Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF-alpha was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (MeWo), leading to the following observations: (i) VZV inhibits the stimulation of icam-1 mRNA synthesis; (ii) despite VZV-induced nuclear translocation of p65, p52, and c-Rel, p50 does not translocate in response to TNF-alpha; (iii) the nuclear p65 present in VZV-infected cells is no longer associated with p50 and is unable to bind the proximal NF-kappaB site of the icam-1 promoter, despite an increased acetylation and accessibility of the promoter in response to TNF-alpha; and (iv) VZV induces the nuclear accumulation of the NF-kappaB inhibitor p100. VZV also inhibits icam-1 stimulation of TNF-alpha by strongly reducing NF-kappaB nuclear translocation in MRC5 fibroblasts. Taken together, these data show that VZV interferes with several aspects of the immune response by inhibiting NF-kappaB binding and the expression of target genes. Targeting NF-kappaB activation, which plays a central role in innate and adaptive immune responses, leads to obvious advantages for the virus, particularly in melanocytes, which are a site of viral replication in the skin. [less ▲]

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See detailWithaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity
Kaileh, Mary; Vanden Berghe, Wim; Heyerick, Arne et al

in Journal of Biological Chemistry (2007), 282(7), 4253

The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major ... [more ▼]

The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major focus of drug development programs. Withania somnifera (WS) is a medicinal plant that is widely used in Palestine for the treatment of various inflammatory disorders. In this study we show that the leave extract of WS, as well as its major constituent withaferin A (WA), potently inhibits NFkappaB activation by preventing the tumor necrosis factor-induced activation of IkappaB kinase beta via a thioalkylation-sensitive redox mechanism, whereas other WS-derived steroidal lactones, such as withanolide A and 12-deoxywithastramonolide, are far less effective. To our knowledge, this is the first communication of IkappaB kinase beta inhibition by a plant-derived inhibitor, coinciding with MEK1/ERK-dependent Ser-181 hyperphosphorylation. This prevents IkappaB phosphorylation and degradation, which subsequently blocks NFkappaB translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our results indicate that pure WA or WA-enriched WS extracts can be considered as a novel class of NFkappaB inhibitors, which hold promise as novel anti-inflammatory agents for treatment of various inflammatory disorders and/or cancer. [less ▲]

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See detailNF-kappa B activation by reactive oxygen species: Fifteen years later
Gloire, Geoffrey ULg; Legrand-Poels, Sylvie ULg; Piette, Jacques ULg

in Biochemical Pharmacology (2006), 72(11), 1493-1505

The transcription factor NF-kappa B plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappa B maybe ... [more ▼]

The transcription factor NF-kappa B plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappa B maybe activated by H(2)o(2), several laboratories have put a considerable effort into dissecting the molecular mechanisms underlying this activation. Whereas early studies revealed an atypical mechanism of activation, leading to I kappa B alpha Y42 phosphorylation independently Of I kappa B kinase (IKK), recent findings suggest that H2O2 activates NF-kappa B mainly through the classical IKK-dependent pathway. The molecular mechanisms leading to IKK activation are, however, cell-type specific and will be presented here. In this review, we also describe the effect of other ROS (HOCl and O-1(2)) and reactive nitrogen species on NF-kappa B activation. Finally, we critically review the recent data highlighting the role of ROS in NF-kappa B activation by proinflammatory cytokines (TNF-alpha and IL-1 beta) and lipopolysaccharide (LPS), two major components of innate immunity. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

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See detailExtending the nuclear roles of I kappa B kinase subunits
Gloire, Geoffrey ULg; Dejardin, Emmanuel ULg; Piette, Jacques ULg

in Biochemical Pharmacology (2006), 72(9), 1081-1089

The transcription factor NF-kappa B plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells ... [more ▼]

The transcription factor NF-kappa B plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells, NF-kappa B is sequestered in the cytoplasm through its tight association with inhibitory proteins called I kappa BS, comprising notably I kappa B alpha. A key step in NF-kappa B activation is the phosphorylation Of I kappa B alpha by the so-called I kappa B kinase (IKK) complex, which targets the inhibitory protein for proteasomal degradation and allows the freed NF-kappa B to enter the nucleus where it can transactivate its target genes. The IKK complex is composed of two catalytic subunits called IKK alpha and IKK beta, and a regulatory subunit called NEMO/IKK gamma. Despite their key role in mediating I kappa B alpha phosphorylation in the cytoplasm, recent works have provided evidence that IKK subunits also translocate into the nucleus to regulate NF-kappa B-dependent and -independent gene expression, paving the way of a novel and exciting field of research. In this review, we will describe the current knowledge in that research area. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

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See detailNF-kappa B activation by double-strand breaks
Habraken, Yvette ULg; Piette, Jacques ULg

in Biochemical Pharmacology (2006), 72(9), 1132-1141

Cellular response to DNA damage is complex and relies on the simultaneous activation of different networks. It involves DNA damage recognition, repair, and induction of signalling cascades leading to cell ... [more ▼]

Cellular response to DNA damage is complex and relies on the simultaneous activation of different networks. It involves DNA damage recognition, repair, and induction of signalling cascades leading to cell cycle checkpoint activation, apoptosis, and stress related responses. The fate of damaged cells depends on the balance between pro- and antiapoptotic signals. in this decisive life or death choice, the transcription factor NF-kappa B has emerged as a prosurvival actor in most cell types. As corollary, it appears to be associated with tumorigenic process and resistance to therapeutic strategies as it protects cancerous cells from death. in this review, we will focus on NF-kappa B activation by double-strand breaks inducing agents, such as ionizing radiation and DNA topoisomerase I and II inhibitors routinely used in cancer therapy. Coinciding with the 20th anniversary of the NF-kappa B discovery, major steps of the DSB-triggered cascade have been recently identified. Two parallel cascades are necessary for NF-kappa B activation. The first one depends on ATM (activated by double-strand breaks) and the second on PIDD (activated by an unknown stress signal). The phosphorylation of NEMO by ATM is the point of convergence of these two cascades. The identification of ATM/NEMO complex as the long searched "nuclear to cytoplasm" signal leading to IKK activation is also a major piece of the puzzle. The knowledge of the precise steps leading to DSB-initiated NF kappa B activation will allow the development of specific blocking compounds reducing its prosurvival function. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

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See detailTNFa and IKKb-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKg and NF-kB activation
Bonif, Marianne; Meuwis, Marie-Alice ULg; Close, Pierre ULg et al

in Biochemical Journal (2006), 394

Pro-inflammatory cytokines trigger signalling cascades leading to NF-kappaB (nuclear factor-kappaB)-dependent gene expression through IKK [IkappaB (inhibitory kappaB) kinase]-dependent phosphorylation and ... [more ▼]

Pro-inflammatory cytokines trigger signalling cascades leading to NF-kappaB (nuclear factor-kappaB)-dependent gene expression through IKK [IkappaB (inhibitory kappaB) kinase]-dependent phosphorylation and subsequent degradation of the IkappaB proteins and via induced phosphorylation of p65. These signalling pathways rely on sequentially activated kinases which are assembled by essential and non-enzymatic scaffold proteins into functional complexes. Here, we show that the pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha) promotes TANK [TRAF (TNF receptor-associated factor) family member associated NF-kappaB activator] recruitment to the IKK complex via a newly characterized C-terminal zinc finger. Moreover, we show that TANK is phosphorylated by IKKbeta upon TNFalpha stimulation and that this modification negatively regulates TANK binding to NEMO (NF-kappaB essential modulator). Interestingly, reduced TANK expression by RNA interference attenuates TNFalpha-mediated induction of a subset of NF-kappaB target genes through decreased p65 transactivation potential. Therefore the scaffold protein TANK is required for the cellular response to TNFalpha by connecting upstream signalling molecules to the IKKs and p65, and its subsequent IKKbeta-mediated phosphorylation may be a mechanism to terminate the TANK-dependent wave of NF-kappaB activation. [less ▲]

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See detailRestoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB activation pathway and cellular survival upon oxidative stress.
Gloire, Geoffrey ULg; Charlier, Edith; Rahmouni, Souad ULg et al

in Oncogene (2006), 25(40), 5485-94

Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have ... [more ▼]

Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have shown that NF-kappaB activation by ROS involved tyrosine phosphorylation of the inhibitor IkappaBalpha through an IkappaB kinase (IKK)-independent mechanism. In the present work, we investigated with more details NF-kappaB redox regulation in human leukemic cells. By using different cell lines (CEM, Jurkat and the subclone Jurkat JR), we clearly showed that NF-kappaB activation by hydrogen peroxide (H2O2) is cell-type dependent: it activates NF-kappaB through tyrosine phosphorylation of IkappaBalpha in Jurkat cells, whereas it induces an IKK-mediated IkappaBalpha phosphorylation on S32 and 36 in CEM and Jurkat JR cells. We showed that this H2O2-induced IKK activation in CEM and Jurkat JR cells is mediated by SH2-containing inositol 5'-phosphatase 1 (SHIP-1), a lipid phosphatase that is absent in Jurkat cells. Indeed, the complementation of SHIP-1 in Jurkat cells made them shift to an IKK-dependent mechanism upon oxidative stress stimulation. We also showed that Jurkat cells expressing SHIP-1 are more resistant to H2O2-induced apoptosis than the parental cells, suggesting that SHIP-1 has an important role in leukemic cell responses to ROS in terms of signal transduction pathways and apoptosis resistance, which can be of interest in improving ROS-mediated chemotherapies. [less ▲]

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See detailPhysical and chemical properties of pyropheophorbide)a-methyl ester in ethanol, phosphate buffer and aqueous dispersion of small unilamellar dimyristoyl-L-a-phosphatidylcholine vesicles
Delanaye, Lisiane; Bahri, Mohamed Ali ULg; Tfibel, Francis et al

in Photochemical & Photobiological Sciences (2006), 5

The aggregation process of pyropheophorbide-a methyl ester (PPME), a second generation hotosensitizer, was investigated in various solvents. Absorption and fluorescence spectra showed that the ... [more ▼]

The aggregation process of pyropheophorbide-a methyl ester (PPME), a second generation hotosensitizer, was investigated in various solvents. Absorption and fluorescence spectra showed that the photosensitizer was under a monomeric form in ethanol as well as in dimyristoyl-L-α-phosphatidylcholine liposomes while it was strongly aggregated in phosphate buffer. A quantitative determination of reactive oxygen species production by PPME in these solvents has been undertaken by electron spin resonance associated with spin trapping technique and absorption spectroscopy. In phosphate buffer, both electron spin resonance and absorption measurements led to the conclusion that singlet oxygen production was not detectable while hydroxyl radical production was very weak. In liposomes and ethanol, singlet oxygen and hydroxyl radical production increased highly; the singlet oxygen quantum yield was determined to be 0.2 in ethanol and 0.13 in liposomes. The hydroxyl radical production origin was also investigated. Singlet oxygen was formed from PPME triplet state deactivation in presence of oxygen. Indeed, the triplet state formation quantum yield of PPME was found to be about 0.23 in ethanol, 0.15 in liposomes (too small to be measured in PBS). [less ▲]

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See detailPerturbation of actin dynamics induces NF-kappa B activation in myelomonocytic cells through an NADPH oxidase-dependent pathway
Kustermans, Gaëlle ULg; El Benna, Jamel; Piette, Jacques ULg et al

in Biochemical Journal (2005), 387(Pt 2), 531-540

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present ... [more ▼]

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-kappa B activation in myelomonocytic cells. The transduction pathway involved the I kappa B (inhibitory kappa B) kinase complex and a degradation of I kappa B alpha. We have shown that NF-kappa B activation in response to the perturbation of actin dynamics required reactive oxygen species. as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O-2(-) release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47(phox). NF-kappa B activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization. [less ▲]

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