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See detailProtein phosphorylation as a key mechanism for the regulation of BCL-3 activity
Viatour, Patrick ULg; Merville, Marie-Paule ULg; Bours, Vincent ULg et al

in Cell Cycle (Georgetown, Tex.) (2004), 3(12), 1498-1501

Constitutive NF-kappaB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas ... [more ▼]

Constitutive NF-kappaB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas, this constitutive NF-kappaB activity is the result of point mutations or translocations of the genes coding for NF-kappaB inhibitors, namely IkappaBalpha or p100. The BCL-3 protein is another member of the IkappaB family and is overexpressed in a subset of human B-cell chronic lymphocytic leukemias because of a chromosomal translocation. This oncoprotein is phosphorylated by multiple kinases including GSK3 and this phosphorylation regulates BCL-3 function by modulating its oncogenic potential and by regulating the expression of a subset of its target genes. Therefore, deciphering the NF-kappaB/IkappaB protein phosphorylations is critical in order to better understand the molecular mechanisms of NF-kappaB-mediated oncogenesis. [less ▲]

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See detailProtein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling
Shin, Young Shik; Remacle, Françoise ULg; Fan, Rong et al

in Biophysical Journal (2011), 100(10), 2378-2386

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See detailProtein stability
Feller, Georges ULg

Conference (2005)

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See detailProtein stability and enzyme activity at extreme biological temperatures
Feller, Georges ULg

in Journal of Physics : Condensed Matter (2010), 22

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See detailProtein Structural Annotation: Multi-Task Learning and Feature Selection
Becker, Julien ULg

Doctoral thesis (2014)

Experimentally determining the three-dimensional structure of a protein is a slow and expensive process. Nowadays, supervised machine learning techniques are widely used to predict protein structures, and ... [more ▼]

Experimentally determining the three-dimensional structure of a protein is a slow and expensive process. Nowadays, supervised machine learning techniques are widely used to predict protein structures, and in particular to predict surrogate annotations, which are much less complex than 3D structures. This dissertation presents, on the one hand, methodological contributions for learning multiple tasks simultaneously and for selecting relevant feature representations, and on the other hand, biological contributions issued from the application of these techniques on several protein annotation problems. Our first methodological contribution introduces a multi-task formulation for learning various protein structural annotation tasks. Unlike the traditional methods proposed in the bioinformatics literature, which mostly treated these tasks independently, our framework exploits the natural idea that multiple related prediction tasks should be designed simultaneously. Our empirical experiments on a set of five sequence labeling tasks clearly highlight the benefit of our multi-task approach against single-task approaches in terms of correctly predicted labels. Our second methodological contribution focuses on the best way to identify a minimal subset of feature functions, {\em i.e.}, functions that encode properties of complex objects, such as sequences or graphs, into appropriate forms (typically, vectors of features) for learning algorithms. Our empirical experiments on disulfide connectivity pattern prediction and disordered regions prediction show that using carefully selected feature functions combined with ensembles of extremely randomized trees lead to very accurate models. Our biological contributions are mainly issued from the results obtained by the application of our feature function selection algorithm on the problems of predicting disulfide connectivity patterns and of predicting disordered regions. In both cases, our approach identified a relevant representation of the data that should play a role in the prediction of disulfide bonds (respectively, disordered regions) and, consequently, in protein structure-function relationships. For example, the major biological contribution made by our method is the discovery of a novel feature function, which has - to our best knowledge - never been highlighted in the context of predicting disordered regions. These representations were carefully assessed against several baselines such as the 10th Critical Assessment of Techniques for Protein Structure Prediction (CASP) competition. [less ▲]

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See detailProtein supply for preterm babies and healthy growth
SENTERRE, Thibault ULg

Scientific conference (2013, June)

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See detailProtein synthesis and folding is a rate limiting step for bacterial growth at low temperatures.
Piette, Florence; D'Amico, Salvino; Leprince, Pierre ULg et al

Poster (2008)

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See detailProtein synthesis and folding is a rate limiting step for bacterial growth at low temperatures.
Piette, Florence; D'Amico, Salvino; Leprince, Pierre ULg et al

Poster (2008)

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See detailProtein tyrosine phosphatases in T cell physiology.
Mustelin, Tomas; Alonso, Andres; Bottini, Nunzio et al

in Molecular Immunology (2004), 41(6-7), 687-700

The molecular mechanisms of signal transduction have been the focus of intense research during the last decade. In T cells, much of the work has centered on protein tyrosine kinase-mediated signaling from ... [more ▼]

The molecular mechanisms of signal transduction have been the focus of intense research during the last decade. In T cells, much of the work has centered on protein tyrosine kinase-mediated signaling from the TCR and cytokine receptors, while the study of protein tyrosine phosphatases has lagged behind. Nevertheless, it has now become clear that many protein tyrosine phosphatases play equally important roles in T cell physiology and that no kinase-regulated system would work without the counterbalancing participation of phosphatases. In fact, we have learned that many processes are regulated primarily on the phosphatase side. This minireview summarizes the current state-of-the art in our understanding of the regulation and biology of protein tyrosine phosphatases in T lymphocyte physiology. [less ▲]

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See detailProtein-Nucleic Acid Recognition: Statistical Analysis Of Atomic Interactions And Influence Of Dna Structure
Lejeune, D.; Delsaux, N.; Charloteaux, Benoît ULg et al

in Proteins-Structure Function and Bioinformatics (2005), 61(2), 258-71

We analyzed structural features of 11,038 direct atomic contacts (either electrostatic, H-bonds, hydrophobic, or other van der Waals interactions) extracted from 139 protein-DNA and 49 protein-RNA ... [more ▼]

We analyzed structural features of 11,038 direct atomic contacts (either electrostatic, H-bonds, hydrophobic, or other van der Waals interactions) extracted from 139 protein-DNA and 49 protein-RNA nonhomologous complexes from the Protein Data Bank (PDB). Globally, H-bonds are the most frequent interactions (approximately 50%), followed by van der Waals, hydrophobic, and electrostatic interactions. From the protein viewpoint, hydrophilic amino acids are over-represented in the interaction databases: Positively charged amino acids mainly contact nucleic acid phosphate groups but can also interact with base edges. From the nucleotide point of view, DNA and RNA behave differently: Most protein-DNA interactions involve phosphate atoms, while protein-RNA interactions involve more frequently base edge and ribose atoms. The increased participation of DNA phosphate involves H-bonds rather than salt bridges. A statistical analysis was performed to find the occurrence of amino acid-nucleotide pairs most different from chance. These pairs were analyzed individually. Finally, we studied the conformation of DNA in the interaction sites. Despite the prevalence of B-DNA in the database, our results suggest that A-DNA is favored in the interaction sites. [less ▲]

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See detailProtein-protein interactions and gene expression regulation in HTLV-1 infected cells.
Legros, Sébastien ULg; Boxus, Mathieu ULg; Dewulf, Jean Francois et al

in Frontiers in Bioscience : A Journal and Virtual Library (2009), 14

Human T-cell leukemia virus type 1 (HTLV-1) propagates in CD4 or CD8 T cells and, after extended latency periods of 30-50 years, causes a rapidly fatal leukemia called adult T-cell leukemia/lymphoma (ATL ... [more ▼]

Human T-cell leukemia virus type 1 (HTLV-1) propagates in CD4 or CD8 T cells and, after extended latency periods of 30-50 years, causes a rapidly fatal leukemia called adult T-cell leukemia/lymphoma (ATL). Infection with HTLV-1 is also associated with a degenerative neuromuscular disease referred to as tropical spastic paraparesis or HTLV-1-associated myelopathy. HTLV genome, in addition to the structural proteins and retroviral enzymes, codes for a region at its 3' end originally designated pX. The products of this region (Tax, Rex, p12I, p13II, p30II and HBZ) play important roles in deregulation of cellular functions by either directly disrupting cellular factors or altering transcription of viral and cellular genes. Here, we will review current knowledge of protein-protein interactions that regulate transcriptional functions of proteins encoded by the pX region. [less ▲]

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See detailProtein-protein interactions and networks: forward and reverse edgetics.
Charloteaux, Benoît ULg; Zhong, Quan; Dreze, Matija et al

in Castrillo, J. I.; Oliver, S. G. (Eds.) Yeast Systems Biology, Methods in Molecular Biology 759 (2011)

Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In ... [more ▼]

Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In interactome networks that are modeled as nodes (macromolecules) connected by edges (interactions), these alterations can be thought of as node removal and edge-specific or "edgetic" perturbations, respectively. Here we present two complementary strategies, forward and reverse edgetics, to investigate the phenotypic outcomes of edgetic perturbations of binary protein-protein interaction networks. Both approaches are based on the yeast two-hybrid system (Y2H). The first allows the determination of the interaction profile of proteins encoded by alleles with known phenotypes to identify edgetic alleles. The second is used to directly isolate edgetic alleles for subsequent in vivo characterization. [less ▲]

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See detailProtéinas placentárias em mamíferos
Melo de Sousa, Noelita; de Figueiredo, José Ricardo; Gonçalves, Paulo Bayard Dias et al

in Ciência Animal (1997), 7(1), 43-55

During the past twenty years, several new placental proteins have been isolated and characterized in woman and several animal species. Among these proteins, it can be mentioned chorionic gonadotrophins ... [more ▼]

During the past twenty years, several new placental proteins have been isolated and characterized in woman and several animal species. Among these proteins, it can be mentioned chorionic gonadotrophins, placental lactogens, interferon tau, pregnancy specific and pregnancy-associated glycoproteins. In spite of the importance of these studies, there are few papers that describe fundamental aspects of these placental proteins such as physical-chemical pregnancy diagnosis methods. Thus, the aim of this report is to present an overview on the major aspects of placental proteins studied up to now, as well as to consider perspectives for their applications in the future in veterinary practice. [less ▲]

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See detailLa protéine JNKBP1 agit comme un régulateur négatif de la signalisation de NOD2 en inhibant son processus d’oligomérisation
Lecat, Aurore ULg

Doctoral thesis (2012)

Le récepteur cytoplasmique NOD2 est l'un des membres les mieux caractérisés de la famille des NLRs. NOD2 est capable de détecter le muramyldipeptide (MDP), un composant de la paroi bactérienne, ce qui ... [more ▼]

Le récepteur cytoplasmique NOD2 est l'un des membres les mieux caractérisés de la famille des NLRs. NOD2 est capable de détecter le muramyldipeptide (MDP), un composant de la paroi bactérienne, ce qui induit les différentes cascades de signalisation conduisant à l'activation de NF-κB, des MAPKs et de l'autophagie. Ces voies contribuent à une réponse immunitaire innée et adaptative efficace. La perte de fonction des mutants NOD2 a été associée à une plus grande susceptibilité à la maladie de Crohn, ce qui souligne l'importance physiologique de la régulation de l'activité de NOD2. Nous avons effectué une étude par une approche protéomique pour rechercher de nouveaux régulateurs de NOD2. Nous avons généré un modèle cellulaire pour cette étude, les cellules HEK293GNV. Nous avons identifié plusieurs nouveaux partenaires de NOD2, dont la protéine JNKBP1 (c-Jun N-terminal kinase binding protein 1), une protéine scaffold caractérisée par un domaine WD40 en amino-terminal. Nous avons aussi débuté la caractérisation d’autres protéines appartenant aux complexes NOD2 purifiés comme ROCK2 (Rho activated kinase 2) et HDAC5 (Histone deacetylase 5). Au vu de nos premiers résultats, les protéines ROCKs sembleraient être des activateurs de la voie NOD2. Nous nous sommes principalement consacrés à l’étude de JNKBP1 qui a été identifiée, en 1999, comme un partenaire et un régulateur positif de JNK. Nous avons montré que JNKBP1 via son domaine WD40, se lie à NOD2 suite à l’activation par le MDP. Cette interaction atténuait l'activation de NF-κB dépendante de NOD2, la synthèse de l'IL-8 et l’activité antibactérienne de NOD2. JNKBP1 exerçait son effet répresseur en perturbant l’oligomérisation NOD2 et la phosphorylation de la tyrosine de RIP2 : deux étapes nécessaires à la signalisation en aval. En outre, nous avons montré que JNKBP1 et NOD2 étaient exprimées dans l'épithélium intestinal humain et dans les cellules immunitaires recrutées dans la lamina propria, ce qui suggère que JNKBP1 contribuerait au maintien de l'homéostasie intestinale dépendante de NOD2. [less ▲]

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See detailLa protéine P53, protectrice de l'intégrité du génome: rôle dans la genèse des cancers
Bellahcene, Akeila ULg; Merville, Marie-Paule ULg; Gielen Jacques et al

in Revue Médicale de Liège (1994), 49(5), 274-84

L'homéostasie des tissus de l'organisme est le résultat d'un équilibre dynamique stable entre des facteurs de régulation positifs et négatifs. Ceux-ci contrôlent la prolifération des cellules et ... [more ▼]

L'homéostasie des tissus de l'organisme est le résultat d'un équilibre dynamique stable entre des facteurs de régulation positifs et négatifs. Ceux-ci contrôlent la prolifération des cellules et déterminent leur appartenance tissulaire. Des données récentes indiquent que l'apparition des cancers résulte du déséquilibre de cet état dynamique soit part l'activation de facteurs positifs désignés sous le terme d'oncogènes, soit par l'inactivation de facteurs négatifs qui sont regroupés dans la famille des gènes suppresseurs de tumeurs. Le gène codant pour la protéine p53 est un membre particulièrement important de cette dernière famille. En effet, son inactivation, par mutation et/ou délétion, est l'une des altérations génétiques la plus fréquemment détectée dans les cancers. La fonction principale attribuée à la protéine p53 consiste à préserver le génome des altérations susceptibles d'entraîner, entre autres, la cellule dans un processus de transformation maligne. C'est en permettant la réparation des altérations du DNA survenues lors de sa réplication avant la mitose ou provoquées par des agents extérieurs, que la protéine p53 semble exercer ses fonctions. Des altérations du gène p53 entraînant des perturbations de la fonction de la protéine p53 ont été identifiées au niveau de la plupart des lésions tumorales malignes. A ce titre, cette protéine semble jouer un rôle déterminant au niveau de la genèse des cancers. Aussi le gène p53 fait-il l'objet de recherches intensives qui devraient déboucher sur la mise au point de nouveaux moyens de détection et d'évaluation pronostique des cancers. D'autre part, des expériences visant à restaurer la fonction de la protéine p53 au niveau des cellules cancéreuses ouvrent de nouvelles et séduisantes perspectives thérapeutiques. [less ▲]

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See detailProtéines alimentaires et fonction rénale
Krzesinski, Jean-Marie ULg

Conference (2001, September 19)

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See detailLes protéines de choc thermique (heat shock proteins). II Les protéines de choc thermique (heat shock proteins). II. Hsp70, biomarqueur, bioprotecteur.
Wirth, Delphine; Gustin, Pascal ULg; Drion, Pierre ULg et al

in Annales de Médecine Vétérinaire (2003), 147(2), 127-144

The exposure of any organism to high temperature induces rapid and transient cellular overexpression of specific proteins, the heat shock proteins (Hsps). This response, called heat shock response, was ... [more ▼]

The exposure of any organism to high temperature induces rapid and transient cellular overexpression of specific proteins, the heat shock proteins (Hsps). This response, called heat shock response, was initially discovered in Drosophila. The genes hsps were among the first eukaryotic genes to be cloned and whose regulation, which involves activation of heat shock factor (HSF), was elucidated. More recently, study of Hsp functions, particularly Hsp70, started. Their protective role, related to their molecular chaperon function, was inferred from experiments showing that Hsp70 expression, induced by a first stress, results in a cellular tolerance to second stress. Better understanding of the heat shock response had led to the development of two search fields on Hsp70 expression : (1) its use as biomarker of cellular stress and (2) the exploitation of its cytoprotective functions against various insults. This review includes historic of the research on the heat shock response, description of regulation mechanism of Hsp70 expression, and the interesting perspectives allocated to Hsp70 as biomarker and therapeutic tool. ----------- L’exposition de tout organisme à des températures élevées induit l'expression cellulaire rapide et transitoire de protéines spécifiques, les protéines de choc thermique (Hsps pour " heat shock proteins "). Cette réponse des cellules au choc thermique ou " heat shock response " a été initialement découverte chez la drosophile. Les gènes hsps furent parmi les premiers gènes eucaryotes à être clonés et utilisés comme paradigme dans l'étude des mécanismes de régulation transcriptionnelle faisant intervenir l'activation d'un ou plusieurs " heat shock factors" (HSFs). C'est plus récemment que l'étude des fonctions des Hsps, particulièrement Hsp70, a débuté. Le rôle protecteur de celle-ci, lié à sa fonction de " chaperon " protéique, a été déduit d'expériences montrant que l'induction de l'expression de Hsp70 lors d'un stress était associée au développement d'une tolérance cellulaire vis-à-vis d'un stress ultérieur. En plus d'un intérêt fondamental pour la compréhension de la "réponse au choc thermique", deux axes de recherche appliquée se sont développés visant à investiguer la possibilité d'utiliser l'expression de Hsp70 comme biomarqueur de souffrance cellulaire d'une part et, d'autre part, d'exploiter ses fonctions comme moyen de protection des cellules contre divers types d'agressions. Cette revue décrit l'historique des découvertes sur la " réponse au choc thermique ", le mécanisme régulant l'expression de Hsp70 ainsi que les perspectives intéressantes s'ouvrant à l'utilisation de l'expression de Hsp70 en tant que biomarqueur et outil thérapeutique. [less ▲]

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