66 research outputs found
Topoisomerase II is regulated by translationally controlled tumor protein for cell survival during organ growth in Drosophila
No full textAbstract: Regulation of cell survival is critical for organ development. Translationally controlled tumor protein (TCTP) is a conserved protein family implicated in the control of cell survival during normal development and tumorigenesis. Previously, we have identified a human Topoisomerase II (TOP2) as a TCTP partner, but its role in vivo has been unknown. To determine the significance of this interaction, we examined their roles in developing Drosophila organs. Top2 RNAi in the wing disc leads to tissue reduction and caspase activation, indicating the essential role of Top2 for cell survival. Top2 RNAi in the eye disc also causes loss of eye and head tissues. Tctp RNAi enhances the phenotypes of Top2 RNAi. The depletion of Tctp reduces Top2 levels in the wing disc and vice versa. Wing size is reduced by Top2 overexpression, implying that proper regulation of Top2 level is important for normal organ development. The wing phenotype of Tctp RNAi is partially suppressed by Top2 overexpression. This study suggests that mutual regulation of Tctp and Top2 protein levels is critical for cell survival during organ development
study of complexes involving TCTP (Translationally Controlled Tumor Protein)
No full textLa 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.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
Etude structurale des complexes entre TCTP (Translationally Controlled Tumor Protein) et ses partenaires anti-apoptotiques Bcl-xl ou Mcl-1
No full textLa 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
Etude des complexes entre TCTP (Translationally Controlled Tumor Protein) et ses partenaires
No full textAdam 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.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
TPT1/TCTP-regulated pathways in phenotypic reprogramming
No full textEvolutionary conserved and pleiotropic, the TPT1/TCTP gene (translationally controlled tumor protein, also called HRF, fortilin), encodes a highly structured mRNA shielded by ribonucleoproteins and closely resembling viral particles. This mRNA activates, as do viruses, protein kinase R (PKR). The TPT1/TCTP protein is structurally similar to mRNA-helicases and MSS4. TPT1/TCTP has recently been identified as a prognostic factor in breast cancer and a critical regulator of the tumor suppressor p53 and of the cancer stem cell (SC) compartment. Emerging evidence indicates that TPT1/TCTP is key to phenotypic reprogramming, as shown in the process of tumor reversion and possibly in pluripotency. We provide here an overview of these diverse functions of TPT1/TCTP
Contribution à l'étude de la génétique moléculaire et de la biologie cellulaire des leucémies
No full textDoctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe
Functional Study of Translationally Controlled Tumor Protein (TCTP) in Different Murine Genetic Models
No full textTCTP est une protéine de 20 kDa que l’on retrouve souvent sous forme de dimère. Elle est fortement conservée dans la phylogénie et on la trouve dans les levures, les plantes, les invertébrés et les mammifères. Elle est localisée dans tous les compartiments de la cellule : noyau, cytoplasme, et membranes. Il s’agit d’une protéine très abondante dans des cellules souches ainsi que des cellules en croissance exponentielle, y compris les cellules tumorales. Sa fonction principale est celle d’une « protéine de survie ». TCTP a été décrite comme interagissant avec de multiples protéines dont p53, MDM2, Bcl-xL et TSAP6. Le but de mon travail est de permettre de mieux caractériser ces fonctions de TCTP et pour cela, nous avons étudié ses interactions in vitro et surtout, in vivo, dans différents modèles génétiques chez la souris.TCTP is a 20 kDa protein frequently encountered as a dimer. It is highly conserved through phylogeny and is present inn yeast, plants, invertebrates and mammals. It is localized in all compartments of the cell: nucleus, cytoplasm, membranes. This protein is highly abundant in stem cells and during the exponential growth, including in cancer cells. It mainly functions as a survivor factor. TCTP has been described as interacting with multiple proteins, including p53, MDM2, Bcl-xL and TSAP6. The purpose of my work is to better characterize these functions of TCTP; we therefore studied its interactions in vitro, but mostly in vivo, using different murine genetic models
The molecular programme of tumour reversion: the steps beyond malignant transformation
No full textInternational audienceHow cells become malignant has preoccupied scientists for over a century. However, the converse question is also valid: are tumour cells capable of reverting from their malignant state? Askanazy's studies in 1907 indicated that teratoma cells could differentiate into normal somatic tissues and current evidence indicates that some tumour cells have acquired the molecular circuitry that results in the negation of chromosomal instability, translocations, oncogene activation and loss of tumour suppressor genes. Studying these extremely rare events of tumour reversion and deciphering these pathways, which involve SIAH1, presenilin 1, TSAP6 and translationally controlled tumour protein (TCTP), could lead to new avenues in cancer treatment
TCTP/tpt1 - Remodeling Signaling from Stem Cell to Disease
No full textInternational audienceIn this brief introduction, we describe our encounter with TCTP. Back in 2000, we discovered TCTP in two quite different ways: first, we looked at protein partners of TSAP6 and one of them was TCTP. Then, in collaboration with Sidney Brenner, we performed a high-throughput differential screening comparing the parental cancer cells with revertants. The results indicated that TCTP was of the most differentially expressed genes. These two approaches were carried out only months apart. They guided our research and led to the discoveries of drugs that inhibit the function of TCTP. Much of the preclinical data on sertraline as an inhibitor of TCTP in cancer were obtained with Judith Karp at Johns Hopkins. This drug is now given in combination with Ara-C to patients in a phase I clinical trial for Acute Myeloid Leukemia. We will here detail how all this happened in our lab while working around one central project: tumor reversion
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