Etude structurale des complexes entre TCTP (Translationally Controlled Tumor Protein) et ses partenaires anti-apoptotiques Bcl-xl ou Mcl-1

La thématique du laboratoire de l équipe d Adam Telerman porte sur la réversion tumorale, un processus rare au cours duquel les cellules cancéreuses perdent leur phénotype malin, et deviennent des cellules dites révertantes. Plusieurs protéines clefs impliquées dans cette transformation ont été mises en évidence, dont TCTP (Translationally Controlled Tumor Protein). La protéine TCTP est également impliquée dans la régulation de l apoptose en interagissant et en renforçant l activité anti-apoptotique de Mcl-1 et de Bcl-xl, deux protéines appartenant à la famille des Bcl-2. Ce projet s attache à comprendre en termes moléculaires le mode d action de TCTP au cours de l apoptose. Dans cet objectif nous nous sommes focalisés sur les modes de reconnaissances entre TCTP et ces deux protéines, Mcl-1 et Bcl-xL. Dans ce contexte nous avons développé une collaboration avec l équipe de Jean Cavarelli du département de biologie structurale intégrative de l IGBMC. Notre objectif a consisté à isoler et à caractériser de façon biochimique, biophysique et structurale les complexes TCTP/Mcl-1 et TCTP/Bcl-xl. Nous avons, après optimisation, déterminé les conditions de formation des complexes TCTP/Mcl-1 et TCTP/Bcl-xl. De façon intéressante, ces complexes sont stables à pH basique, faible concentration ionique et favorisés par chauffage. Grâce à une analyse combinée par ultracentrifugation analytique, SEC-MALS et spectrométrie de masse en condition native, nous avons pu déterminer la formation d hétérotétramères de TCTP/Mcl-1 et de TCTP/Bcl-xl. Nous avons également pu identifier les domaines d interaction de ces complexes par mutagénèse dirigée, et montrer que la partie N terminale de TCTP et le sillon hydrophobe de Bcl-xl sont impliqués dans ces interactions. Il s agit de la première caractérisation biochimique et biophysique de complexes impliquant TCTP. Ces données fournissent les premières bases pour l étude structurale de complexes avec TCTP.Adam Telerman s team research focuses on tumor reversion, a rare process in which cancer cells lose their malignant phenotype, and therefore become revertant. Many key proteins were showed to be involved in this transformation, including TCTP (translationally Controlled Tumor Protein). TCTP protein is also involved in apoptosis regulation by interacting and strengthening the anti-apoptotic activity of Mcl-1 and Bcl-xl, two proteins from Bcl-2 family. This work is dedicated to understand the molecular mechanism underlying TCTP action in apoptosis. Here, we focus on TCTP/Mcl-1 and TCTP/Bcl-xl complexes. Within a collaboration with the team of Jean Cavarelli from the department of integrative structural biology at IGBMC we managed to isolate and determine the biochemical properties of these complexes. We showed that TCTP:Mcl1 and TCTP:Bcl-xL have the particularity to be sensitive to pH, ionic strength and temperature. Using analytical ultracentrifugation, SEC-MALS and native mass-spectrometry we were able to characterize both complexes and localize their binding interface. TCTP:Mcl1 and TCTP:Bcl-xL can form heterotetramers, involving the N-terminal part of TCTP and the BH3-groove of Bcl-xL. This work provides the first biophysical and biochemical study of complexes involving TCTP and can be used as a basis for further structural studies on TCTP complexes.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Modèles d’ordre réduit pour l’analyse et la modélisation de l'effet cheminée et des transferts de chaleur associés - application aux enveloppes ventilées des bâtiments solaires ou producteurs d’énergie

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Canal vertical uniformément chauffé soumis à différentes stratifications thermiques extérieures – Etude expérimentale et numérique

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Natural convective flow analysis in vertical channel

International audienc

Natural convective flow analysis in vertical channel

International audienc

Chimney effect analysis for wall thermal flux injection

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Impact of external temperature distribution on the turbulent and thermal fields in a vertical uniformly heated channel

International audienc

Detailed flow development and indicators of transition in a natural convection flow in a vertical channel

International audienceA spatially developing transitional flow in a vertical channel with one side heated uniformly and subjected to random velocity fluctuations at theinlet is investigated in this experimental and numerical study. Two Rayleigh numbers are studied. Experimentally, Particle Image Velocimetry is used to obtain a complete two-dimensional velocity field of the streamwise flow development. A three-dimensional Large-Eddy-Simulation investigation isalso performed to obtain a complete streamwise evolution of the flow. The results allow the denition of three transition indicators on the basis of thetime-averaged velocities and temperatures elds as well as on the turbulent statistics of the flow. The detailed experimental and numerical spatial development of the transitional natural convective flow is then presented and the ability of the indicators to capture the early and the advanced stages of the transition is assessed. The numerical simulations were performed on the assumptions of a thermally stratied environment, submitted to an environmental noise, and for which wall to wall radiations were considered. These conditions aim at representing realistic experimental conditions

Impact of external temperature distribution on the convective mass flow rate in a vertical channel – A theoretical and experimental study

International audienceMany works have been performed on heated vertical rectangular open-ended channels. Whilst in most cases, thermal fields are quite well predicted or reproducible, there were often large unexplained variations in the experimental flow rate for apparently the same conditions. An experimental and theoretical investigation has therefore been carried out to identify the effect of external thermal stratifications on the flow rate. Four values of steady and uniform heat flux, equivalent to Rayleigh numbers between 2.9×104 and 1.6×108 were imposed experimentally either on one or both sides of a vertical rectangular channel, with various ambient thermal gradients external to the channel. It was observed that the mass flow rate was significantly reduced as the positive upward, external thermal gradient increased. A theoretical model of the phenomenon was also developed. There is an excellent agreement between the theoretically predicted and experimentally measured mass flow rates. This clearly highlights that external temperature distributions are key driving factors and their influence is accurately quantified in this work

Assessment of decomposition methods for the analysis of transitional natural convection flow in a vertical channel

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