Dissertationen zum Thema „Récepteurs nucléaires à l'Acide Rétinoïque“
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Mouchon, Arnaud. „Modulation de l'activité des récepteurs à l'acide rétinoïque par des interactions moléculaires“. Lille 1, 1999. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/1999/50376-1999-191.pdf.
Der volle Inhalt der QuelleL'ensemble des résultats obtenus par la suite identifie la région 403-410 comme essentielle pour l'activité biologique du récepteur, pour la liaison aux ligands, pour le recrutement des co-activateurs ou co-répresseur et de ce fait, essentielle dans l'interprétation de la pharmacologie des rétinoïdes (B. Lefebvre et al. , Mol. Cell. Endocrinol 1998a ; B. Lefebvre et al. , Biochemistry 1998b). Nous avons enfin montré que la capacité des ligands naturels et synthétiques à induire l'activité transcriptionnelle d'un gène chimérique est proportionnelle à leur capacité à recruter le co-activateur SRC1. Outre la structure du ligand, nous avons observé que l'ADN et le RXR exerçaient des régulations allostériques sur ces interactions protéines-protéines (A. Mouchon et al. , Mol. Cell. Biol. 1999). L'ensemble de ces résultats identifie la région 403-410 du hRAR[alpha] comme essentielle pour l'activité biologique du récepteur, par son implication dans la liaison et l'interprétation de la pharmacologie des ligands ; de plus, la structure du ligand a un effet considérable sur les transitions de structure que subit le RAR dans le contexte de l'hétérodimère lié à l'ADN, structure qui est également modulée par la structure du RARE et vraisemblablement par RXR
Martin, Perrine. „Recherche de nouveaux partenaires protéiques du Récepteur de l'Acide Rétinoïque : étude des interactions RAR-PLZF et RAR-PCNA“. Lille 2, 2005. http://www.theses.fr/2005LIL2S003.
Der volle Inhalt der QuelleThe Retinoic Acid Receptors (RAR) interact, in a ligand-dependent manner, with many coregulators which are involved in a broad spectrum of biological responses, from embryonic development to cell growth control. The transactivation function of these ligand-inducible transcription factors resides mainly, but not exclusively, in their Ligand Binding Domain (AF2) which recruits or dissociates coregulators in a ligand-dependent manner. Nevertheless, the RAR AF2-independent functions are not much elucidated. In this study, we have identified, by yeast two-hybrid screen, new RARa two partners, the PLZF (Promyelocytic Leukemia Zinc Finger) and PCNA (Proliferating Cell Nuclear Antigen) proteins. These two proteins interact physically and functionally with the RARa and act as RARa repressors. In addition, they have very distinct functions and exert their repressor effect through different domains and via different mechanisms. We have demonstrated that PLZF interferes probably with RAR-RXR dimerization. In contrast, PCNA interacts with RAR-RXR heterodimer bound to its response element and represses its transcriptional activity in a promoter- and cell-specific manner. These observations demonstrate new mechanisms by which RARa activity is controlled, and suggest a link between RARa, embryonic development and hematopoiesis in the case of PLZF and between RARa, cell cycle and DNA repair in the case of PCNA
Lalevée, Sébastien. „Les récepteurs nucléaires de l’acide rétinoïque : phosphorylation et contrôle dynamique de l’association-dissociation de complexes protéiques“. Strasbourg, 2009. https://publication-theses.unistra.fr/public/theses_doctorat/2009/LALEVEE_Sebastien_2009.pdf.
Der volle Inhalt der QuelleThe effects of Retinoids (active derivatives of Vitamin A) are mediated by two families of nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ). In vivo, the RA signal is transmitted by RAR/RXR heterodimers, which function as ligand‐dependent transcriptional regulators and bind to RARE (Retinoic Acid Response Element) at the promoters of target genes. Our team demonstrated that two domains of RARs, the NTD (N‐terminal Domain) and the LBD (Ligand Binding Domain), are targets for phosphorylation processes that control RAR transcription. In order to decipher how phosphorylation controls RARs functions, I analyzed the dynamics of RAR (α and γ) association/dissociation with different protein partners depending on RARs phosphorylation state. In the case of RARα, I highlighted the consequences of LBD phosphorylation at serine 369, localized in close vicinity to the cyclin H docking site. This phosphorylation, via conformational changes, influences the recruitment of cyclin H associated to the cdk7 kinase of the general transcription factor TFIIH. This effect is at the basis of a cascade leading to the phosphorylation of the NTD by cdk7. I also participated to the study of another RARα partner, SUG‐1, a subunit of the proteasome. SUG‐1 plays a dual role in RARα target gene transcription by regulating the dynamic of transcription without proteolysis and by signaling the end of the RA response via the degradation of its coactivator, SRC‐3. In the case of RARγ, I demonstrated that the PRM (Proline Rich Motif) of the NTD interacts directly with one SH3 domain of Vinexin β, an adaptor protein. This association occurs only when the PRM is not phosphorylated and maintains the receptor outside of the chromatin. After RA addition, one of the serine of the PRM becomes phosphorylated, inducing the dissociation of Vinexin β, and finally the recruitment of phosphorylated RARγ to RA target‐genes. In this context, I also realized a “genome wide” bioinformatic search for finding new functional RAREs
Kammerer, Sabrina Myriam. „Etude structurale de l'interaction récepteurs nucléaires/corégulateurs et du domaine de liaison au ligand du récepteur à l'acide rétinoïque“. Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13206.
Der volle Inhalt der QuelleNuclear receptors (NR) are ligand dependant transcription factors which share a common modular organization. The A/B domain bears the autonomous activation fonction AF1. The C domain is the DNA binding domain (DBD). The D domain contitutes a hinge between the C- and E domain. The E domain is the ligand binding domain (LBD) which also bears the ligand-dependant activation fonction AF2. NR plays an important role in the regulation of cell proliferation, differentiation, apoptosis and in cell homeostasis maintenance. Thus they are targeted by numerous treatment notably by cancer therapy, and by diabet and obesity treatments. Numerous studies uncovered the canonical three dimensional fold of LBD as well as the structural basis of agonism/antagonism. But at the begining of my PhD, the structural basis of corepresseur recruitment as well as the structural mechanism of AF1 fonction were unknown. To adress these questions we decided to undergo the two first projects of my PhD
Bruck, Nathalie. „Phosphorylation des récepteurs nucléaires de l'acide rétinoïque : Mécanisme et conséquences sur la transcription des gènes cibles“. Université Louis Pasteur (Strasbourg) (1971-2008), 2008. http://www.theses.fr/2008STR13134.
Der volle Inhalt der QuelleVernet, Nadège. „Analyse du rôle de l'acide rétinoïque et de ses récepteurs au cours de la spermatogenèse“. Université Louis Pasteur (Strasbourg) (1971-2008), 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/VERNET_Nadege_2006.pdf.
Der volle Inhalt der QuelleIt has been known for more than a decade that retinoic acid (RA) is indispensable for the differentiation of spermatogonia, the stem cells of the spermatogenic lineage. RA acts though binding to nuclear receptors, the RAR and the RXR, which in the mouse testis have very distinct expression patterns. In particular, we detected RARg only in spermatogonia while RARa is present only in Sertoli cells, the somatic cells supporting the gem cell lineage. Selective inactivation of RARa in Sertoli cells (RaraSer-/- mutation) results in a testicular degeneration through germ cell desquamation and apoptosis. Sertoli cells lacking RARa are morphologically normal. However, they fail to express genes involved in cell adhesion (Lgals1) and loose the property to cyclically express genes encoding transcription factors (Gata1, Androgen receptor gene), membrane and secreted proteins (e. G. , Stra6). These data indicate at the very least that Rara expression in Sertoli cells is instrumental to the maintenance of the seminiferous epithelium. On the other hand, we showed that RaraSer-/- mutant mice do not recapitulate the arrest of spermatogonia maturation which we described in a situation of vitamin A-deficiency (VAD). The reasons of the differences between the VAD-induced testicular degeneration and those caused by Rara ablation are still unknown. Moreover, we revealed that, in Sertoli cells, RARa will act in RXRb-heterodimer to control spermiation and that RARa also exerts functions (Sertoli cell cycle, seminiferous epithelium integrity) independently of RXRs
Rachez, Christophe. „Détermiants structuraux du récepteurs humain alpha de l'acide rétinoïque (RAR) impliqués dans la dimérisation et la liaisin à l'ADN“. Lille 1, 1996. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/1996/50376-1996-89.pdf.
Der volle Inhalt der QuelleCoustaut, Maryse. „Expression des récepteurs nucléaires de l'acide rétinoïque et de la triiodothyronine au cours du vieillissement et d'une alcoolisation chronique“. Bordeaux 1, 1996. http://www.theses.fr/1996BOR10588.
Der volle Inhalt der QuellePiskunov, Aleksandr. „Le récepteur nucléaire de l'acide rétinoïque alpha (RARa) : nouveaux effets non-génomiques et nouveaux partenaires“. Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00756292.
Der volle Inhalt der QuelleFerry, Christine. „Activité protéolytique et non protéolytique du protéasome et de ses sous-complexes dans la réponse à l’acide rétinoïque“. Strasbourg, 2010. http://www.theses.fr/2010STRA6220.
Der volle Inhalt der QuelleThe effects of Retinoids (active derivatives of Vitamin A) are mediated by two classes of nuclear receptors, RAR (α, β, γ) and RXR (α, β, γ), which function as ligand‐dependent transcription regulators. The team demonstrated that the transcriptional activity of RARα is regulated by phosphorylation processes and by the dynamic recruitment of coregulators like SRC‐3 and of proteasomal subunits such as SUG‐1. Moreover, RARα and its coactivator SRC‐3 are degraded by the proteasome at the end of the retinoid signal. I participated to the study of non‐genomic effects of RA, initiated by kinase cascades leading to RARα phosphorylation at two serine residues (S369 and S77) and to RARα recruitment to the promoters of target genes. Then I investigated how phosphorylation and the proteasome regulate SRC‐3 activity. I have shown that SRC‐3 is recruited concomitantly with SUG‐1 to RARα target promoters and that both of them participate to the dynamics of transcription. Then, I have shown that SRC3 is phosphorylated, ubiquitinated and degraded by the proteasome. The phosphorylated residue has been identified as Serine 860. By using a siRNA hightroughput screen I identified Cullin 3 and Rbx1 as components of the E3 ligase involved in the ubiquitination/degradation of SRC‐3. In addition SRC‐3 ubiquitination depends on S860 phosphorylation and occurs out of chromatin subsequently to SRC‐3 dissociation from RARα. Finally, the proteasomal degradation of SRC‐3 also involves SUG‐1. Concerning RARα, it appears that its degradation is more complex and does not involve the classical models. Nevertheless, S369 phosphorylation and the coactivators binding surface appears to be involved. In conclusion, I highlighted a global role of the proteasome in the RA response as it is implicated in the initiation of target genes transcription as well as in the degradation of RARα and SRC‐3
Bastien, Julie. „Etude des voies de signalisation interférant avec la voie des rétinoïdes : Conséquences sur la phosphorylation et l'activité des récepteurs nucléaires de l'acide rétinoïque“. Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13133.
Der volle Inhalt der QuelleAgadir, Anissa. „Récepteurs nucléaires de l'acide rétinoïque et concentrations cellulaires efficaces : implication dans la réponse au traitement différenciateur des leucémies aiguës promyélocytaires“. Paris 5, 1995. http://www.theses.fr/1995PA05CD04.
Der volle Inhalt der QuelleVallortigara, Julie. „Etude des effets de l'hypothyroïdie sur les voies d'action cellulaire de l'acide rétinoïque et de la triiodothyronineApproches expérimentale et biomédicale“. Bordeaux 1, 2007. http://www.theses.fr/2007BOR13395.
Der volle Inhalt der QuelleSeveral works permit to establish a relationship between activity of retinoic acid (RA) pathway and memory performance. Recent data obtained in vitamin A deficient (VAD) animals, comparable to those obtained in aged animals, have revealed that RA promnesic effect in brain tissues could depend on thyroid hormone status. Indeed, in these models, triiodothyronine (T3) becomes a limiting factor alone able to correct the age or VAD-related concomitant hypo-activation of retinoid and thyroid signalling and alterations of synaptic plasticity. The aim of the present study was to investigate the effects of hypothyroidism on RA and T3 cellular action in adult mice brain. Our results show that hypothyroidism led to a reduced expression of T3 nuclear receptors (TRβ) and their target genes (RC3, Rhes, CaMKII) preferentially in the striatum. RA administration has no incidence in our model, confirming an impaired function of RA with hypoactivity of T3 signalling. In addition, T3 administration permitted a restoration of molecular parameters studied, and modified phospho-Thr34 DARPP-32 protein level, a reliable indicator of synaptic plasticity involved in motor functions. A study using transgenic animals has revealed that normalization of synaptic target genes by the T3 necessitates the presence of the receptor TRα. These results provide new data regarding the molecular basis of thyroid hormone action in the synaptic plasticity process. A biomedical approach performed on peripheral blood mononuclear cells of hypothyroid patients allowed us to confirm in humans the relevance of the relationship between retinoid and thyroid signalling pathways during common thyroid disorders
Raverdeau, Mathilde. „Etude fonctionnelle de la voie de signalisation de l'acide rétinoïque au cours de la spermatogenèse“. Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ034.
Der volle Inhalt der QuelleRetinoic acid (RA) is required for many physiological functions including reproduction. It is synthesized by retinaldehyde dehydrogenases (RALDH1 to 3) and activates transcription of target genes by binding to its nuclear receptors (RAR α,β,γ ). The purpose of my thesis was to study the functions of RA produced in testicular Sertoli cells in spermatogenesis in the mouse. Thus, by studying the effects of RALDH selective inactivation in murine Sertoli cells by somatic mutagenesis, I showed that Sertoli cells direct the first differentiation of germ cells through their production of RA, which is then dispensable for the proper conduct of spermatogenesis. Induction of the first spermatogenesis is possible by selective activation of RAR, which is at the basis of several signaling pathways. I also confirmed the crucial role of the RA pathway in Sertoli cells for spermiation, the final stage of spermatogenesis, and therefore fertility. Finally, I demonstrated the need of an in vivo RA signaling for meiosis, which controls the expression of Stra8, a gene essential for meiotic progression. This regulation is done cell-autonomously and requires the binding of a RAR on its response element located in the promoter region of Stra8
Koshy, Aysis. „Characterization of Neural Development : Linking Retinoic Acid Receptors to Cell Fate and Modelling Tumorigenesis in Brain Organoids“. Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL119.
Der volle Inhalt der QuelleThe development of the Central Nervous system in the embryo depends on timely and precise signaling of molecules. Retinoic acid is one such molecule well characterized for its impact in brain and eye development. In its metabolically active form, ATRA (All Trans Retinoic acid) binds Retinoic acid receptors (RAR), and controls downstream gene expression attributed to cell maturation and apoptosis. The RAR exists as three isotypes - RARα, RARβ, & RARγ. During embryological development, each isotype is present in spatially distinct locations influencing patterning and maturation. The current state of research is limited to the correlation of a specific RAR isotype to a particular cell fate. In this thesis, we discuss findings that point to the ability of RARβ & RARγ to synergistically restore cell specialization by hijacking RARα-controlled gene programs. In a single-cell RNAseq approach, we are able to visualize several clusters unique to RARβ + RARγ activation during mouse stem cell differentiation beyond neuronal precursor stages. In a similar vein, studying nervous tissue development in the context of diseases is relevant to understanding disease characteristics and identifying targeted therapy options. With this in mind, we wanted to develop a mouse brain organoid (BORG) model from H3.3K27M and H3.3G34R mutant mouse ES cells as an invitro research model that is cost effective and reproducible. Here, we show proof of a tumorigenic like mouse BORG that harbors a TP53 knockout signature
Amal, Ismail. „Étude in silico de la régulation allostérique du récepteur à l’acide rétinoïque par phosphorylation“. Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ029.
Der volle Inhalt der QuelleRetinoic Acid (RA) plays a critical role in many cellular processus through regulatory effects on cellular differentiation, proliferation and apoptosis. This proprety is at the basis of RA therapy in the treatment of several diseases and cancers such as Acute Promyelocytic Leukemia. Deciphering how RA controls the expression of specific subsets of genes is therefore a permanent challenge in oncology. The effects of RA are mediated in vivo by the retinoic acid receptor (RAR), which consistsof three subtypes. A new concept has recently emerged according to which phosphorylation of RARs by different kinases is a necessary step in the regulation of their function. In this context, the specific aim of this thesis was the elucidation of the molecular mechanisms of the regulation of RAR mediated by phosphorylation. In particular, we focused on two aspects, the effects of phosphorylation of the ligand binding domain (LBD) and the effects on the N-terminal domain (NTD). In the case of the LBD, phosphorylation enhanced binding to cyclin H, a component of the TFIIH transcription factor, while phosphorylation of the NTD decreased binding to vinexinB, a corepressor protein. We used molecular dynamics simulations to characterize the structural dynamics of these proteins in both phosphorylated and unphosphorylated states and to quantify theirinteractions. From this project, we were able to define the molecular basis of the communication between RA-induced phosphorylation cascades and regulatory mechanisms of high importance
Samarut, Eric. „Etude fonctionnelle et évolutive de la voie de l'acide rétinoique et de la phosphorylation des récepteurs chez le poisson zèbre“. Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ046/document.
Der volle Inhalt der QuelleRetinoic acid (RA) is the main active metabolite of vitamin A and plays multiple roles in cellular processes but also during embryonic development. RA acts through two families of nuclear receptors: Retinoic Acid Receptors (RAR) and Retinoid X Receptors (RXR). Those receptors act as ligand-dependent transcription factors and their transcriptional activity is also regulated by phosphorylation processes through kinases activated by RA. During my PhD, I focused on the functional and evolutionary study of RA pathway and of the phosphorylation of RARs using zebrafish (Danio rerio). By studying the activity of the different RAR subtypes in zebrafish, we provide evidences that they can regulate gene expression in a subtype-specific fashion in the early zebrafish embryo. Furthermore, my work showed that during evolution, the acquisition of a phosphorylated residue in RARα promotes the fine-tuned regulation of its activity in mammals. Finally, aiming at deciphering the molecular mechanisms behind dentition diversification in fish, we propose a role for RA signaling in generating morphological novel traits during evolution
Douziech-Eyrolles, Laurence. „Synthèse d'agonistes et antagonistes des récepteurs de l'acide rétinoïque“. Paris 5, 1994. http://www.theses.fr/1994PA05P625.
Der volle Inhalt der QuelleDepoix, Christophe. „Régulation de l'activité des récepteurs de l'acide rétinoi͏̈que par la dimérisation“. Lille 2, 2002. http://www.theses.fr/2002LIL2MT01.
Der volle Inhalt der QuelleSeguin, Devaux Carole. „Implication des récepteurs à l' acide rétinoi͏̈que et aux rétinoi͏̈des X dans la modulation de certaines composantes de la réaction immunitaire chez le rat“. Nancy 1, 2001. http://www.theses.fr/2001NAN11313.
Der volle Inhalt der QuelleToulouse, André. „Étude de l'implication des récepteurs de l'acide rétinoïque dans le contrôle de la tumorigénèse pulmonaire“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ35646.pdf.
Der volle Inhalt der QuellePicard, Evelyne. „Caractérisation de l'expression des récepteurs de l'acide rétinoïque et de rétinoïdes X dans le cancer bronchique“. Nancy 1, 1999. http://www.theses.fr/1999NAN19916.
Der volle Inhalt der QuelleBaniowska, Monika. „Rôle de la signalisation par l'acide rétinoïque dans le développement et les fonctions du system dopaminergique nigro-striée“. Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00923148.
Der volle Inhalt der QuelleHaushalter, Carole. „Rôle de l'acide rétinoïque dans la neurogenèse corticale chez la souris“. Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ063/document.
Der volle Inhalt der QuelleRetinoic acid (RA), an active vitamin A (retinol) metabolite, is a small lipophilic molecule controlling numerous events during central nervous system development in vertebrates. RA is involved in early forebrain development by controlling cell proliferation and survival in the prosencephalic neuroepithelium. Neural development is a process progressing through three key steps: a phase of lateral expansion (E9.5-E10.5 in the mouse), a phase of neurogenesis (E11.5-perinatal stages) and a gliogenic phase (perinatal stages-adult). My work has shown that RA produced by the developing meninges from E13 influences neuronal specification and migration during the phase of neurogenesis. Moreover, our data suggest an earlier role of RA during the production and proliferation of progenitor and neuronal populations, before and at the onset of the neurogenic phase. A combination of extrinsic and intrinsic signals is required to orchestrate the various aspects of cortical development. RA is likely to be one of such extrinsic factors modulating cortical neurogenesis
Ricaud, Stéphanie. „Implication de la myostatine et des récepteurs de l'acide rétinoïque dans la dérégulation du programme myogénique des rhabdomyosarcomes humains“. Montpellier 2, 2004. http://www.theses.fr/2004MON20014.
Der volle Inhalt der QuelleCarrier, Marilyn. „Dérégulation du phosphoprotéome dans les cancers : conséquences sur l'activité transcriptionnelle et la dégradation des récepteurs de l'acide rétinoïque (RAR)“. Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ012/document.
Der volle Inhalt der QuelleRetinoic acid (RA) acts by binding to specific nuclear receptors (RARs), which are ligand-dependant transcription factors. RA also has non-genomic effects and activates kinase cascades that target RARs and modulate their transcriptional activity. However, the proteins that are phosphorylated in response to RA remain to be identified. The consequences of dysregulations of the "kinome" on the non-genomic effects of RA and on RAR function also require further investigation. I compared the effect of RA on the phosphoproteome of two breast cancer cell lines: MCF7, which is RA-sensitive, and BT474, a RA-resistant cell line that overexpresses the receptor tyrosine kinase erbB-2. Multiple differences were observed with consequences on gene expression as well as on phosphorylation, recruitment on target genes promoters and RARalpha degradation by the proteasome. In the context or RARalpha degradation, I showed the involvement of TRIM24 which controls RARα deubiquitination
Robert, Carine. „Etude de l'apoptose induite par l'acide rétinoique tout-trans, dans un modèle de leucémie à éosinophiles : implication dans le traitement des syndromes hypereosinophiliques“. Paris 7, 2006. http://www.theses.fr/2006PA077161.
Der volle Inhalt der QuelleHypereosinophilic syndrome/chronic eosinophilic leukaemia (HES/CEL) is a life threatening disease due to infiltration of vital organs by excessive amounts of eosinophils. The discovery of the imatinib mesylate (Evl)-inhibitable FIPILl/PDGFRa (F/P) oncogenic tyrosine kinase fusion protein, observed in 50% of cases of CEL, permitted to treat F/P-positive CEL with IM successfully. However, acquired, as well as de novo résistance to IM have been described in CEL. In order to further improve the treatment of HES/CEL, we investigated the effects of all-trans retinoic acid (ATRA) on the EoL-1 cell line, the only relevant in vitro tool currently available for the study of F/P-positive CEL, and on eosinopoiesis of CEL-derived bone marrow cells ex vivo. We have shown that ATRA (i) potently induces the apoptosis of the F/P-positive EoL-1 cell line by a mechanism dependent on retinoic acid receptor a activation, (ii) selectively inhibits eosinophil colony formation in semisolid cultures of bone marrow mononuclear cells obtained from patients with F/P-positive CEL, (iii) in combination with imatinib or other tyrosine kinase inhibitors, induces apoptosis in EoL-1 cells with greater potency than when any of the drugs is used alone, and (iv) induces the apoptosis of IM-resistant cells derived from the EoL-1 cell line. Our results indicate that the combination of ATRA, a drug already in use in the clinic for acute promyelocytic leukaemia, with IM-type tyrosine kinase inhibitors may significantly enhance the efficacy of the anti-leukaemic treatment of de novo HES/CEL, and that ATRA may prove useful even in tyrosine kinase-resistant HES/CEL
Buaud, Benjamin. „Apports en acides gras et voie de signalisation des récepteurs nucléaires aux rétinoïdes dans le cerveau“. Bordeaux 1, 2007. http://www.theses.fr/2007BOR13541.
Der volle Inhalt der QuelleDespouy, Gilles. „Identification de nouvelles voies de régulation de l'activation transcriptionnelle par les récepteurs nucléaires à l'acide rétinoi͏̈que“. Paris 7, 2002. http://www.theses.fr/2002PA077205.
Der volle Inhalt der QuelleBourguet, William. „Synthèse de nouveaux ligands utilisables pour la purification des récepteurs de l'acide rétinoïque et l'étude du mode d'action des rétinoïdes“. Lille 1, 1992. http://www.theses.fr/1992LIL10160.
Der volle Inhalt der QuellePendaries, Valérie. „Interaction ligand-dépendante entre les récepteurs de l'acide rétinoi͏̈que et le voie de signalisation du TGF-Beta par les Smads“. Paris 7, 2003. http://www.theses.fr/2003PA077249.
Der volle Inhalt der QuelleMailfait, Sandrine. „Le récepteur alpha de l'acide rétinoique : résidus déterminants du site de liaison et rôle dans le mécanisme d'activation“. Lille 1, 1998. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/1998/50376-1998-197.pdf.
Der volle Inhalt der QuelleDevaux, Yvan. „Vitamine A et interactions hote-pathogène : effets de l'acide retinoique sur certaines composantes de la réaction immunitaire chez le rat“. Nancy 1, 2001. http://www.theses.fr/2001NAN11312.
Der volle Inhalt der QuelleGrandemenge-Arnould, Cécile. „Caractérisation d'une fusion génique originale au cours d'une leucémie aiguë promyélocytaire atypique : STAT5b, nouveau partenaire du gène codant le récepteur [alpha] de l'acide rétinoïque“. Nancy 1, 1999. http://www.theses.fr/1999NAN19911.
Der volle Inhalt der QuelleAcute promyelocytic leukaemia (APL) exhibits a characteristic t(15;17) translocation that fuses the PML gene on 15q22 to the retinoic acid receptor [alpha] (RARA) gene on 17q12-q21. 1. In a small subset of acute promyelocytic-like leukaemias (APL-L), RARA is fused to a different partner: PLZF, NPM or NuMA. We report on the molecular characterization of a RARA gene rearrangement in a patient with an APL-L associated with a der(17). Thanks to the 5' RACE PCR approach, we demonstrate that the Signal Transducer and Activator of Transcription STAT5b gene is fused to RARA; STAT5b belongs to a family of latent cytosolic transcription factors activated by JAK tyrosine kinases
Drujont, Lucile. „Étude de nouveaux acteurs de l'immunité de type 17 à travers l'exploration du rôle des canaux ioniques TMEM176A et B dans les cellules RORγt+“. Nantes, 2016. https://archive.bu.univ-nantes.fr/pollux/show/show?id=36471303-ef4e-453c-94a1-59fb808e17a9.
Der volle Inhalt der QuelleThe nuclear hormone receptor RORγt is the key transcription factor that orchestrates the differentiation of Th17 cells but also defines γƠT17 cells and group 3 Innate Lymphoid Cells (ILC3s). We identified TMEM176B, a fourspan transmembrane protein that interacts with its structurally identical homolog protein TMEM176A. Electrophysiological experiments revealed that TMEM176A and B function as cation channels and can heteromerize to exert their function. Strikingy, these two homologs were found among the few direct targets of RORγt. We show that both genes are highly expressed in in vitro-generated mouse Th17 cells compared to Th1, Th2 or iTregs. We also observed that human Th17 cells strongly express TMEM176A and B mRNA, correlating with the level of RORC or IL17A. We further demonstrate that Tmem176a and b are highly expressed in ILC3s and γƠT17 cells. We thus hypothesized that these genes could play a crucial role in the development of a variety of autoimmune diseases dependent on RORγt+ cells. In this regard, Tmem176bdeficient mice were partially but significantly protected from psoriasis-like lesions when compared to control mice. These results suggest that the deletion of both genes may be required to clearly elucidate their role. We have successfully generated a double KO mouse and started to assess the impact of this double deficiency in the steady states as well as in models of inflammation. In parallel, we found that TMEM176A and B protein localizations are strongly linked to the Golgi apparatus, thus highlighting novel potential mechanisms of post-translational modifications or intracellular trafficking in which these cation channels could be involved. We believe that the study of TMEM176A and B will help decipher novel specific pathways of the RORYt+ cell biology that could be therapeutically manipulated
Boucheron, Catherine. „Etude des effets de la consommation d'alcool sur l'action cellulaire de l'acide rétinoi͏̈que et de la triiodothyronine en fonction de l'âge : approches expérimentale et biomédicale“. Bordeaux 1, 2004. http://www.theses.fr/2004BOR12826.
Der volle Inhalt der QuelleLakhlef, Ratiba. „Régulation transcriptionnelle de l'expression du gène de la molécule d'adhésion intercellulaire-1 (ICAM-1) par l'interaction entre les récepteurs à l'acide rétinoïque et les rcepteurs thyroïdiens“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0004/MQ44685.pdf.
Der volle Inhalt der QuelleSt-Jean, Stéphanie. „La transcription du gène PEDF est contrôlée par le corépresseur NCOR1 au niveau des cellules épithéliales intestinales et PEDF agit comme un gène suppresseur de tumeur“. Mémoire, Université de Sherbrooke, 2011. http://savoirs.usherbrooke.ca/handle/11143/4074.
Der volle Inhalt der QuelleBlanchet, Sandrine. „Role des récepteurs nucléaires (RAR) de l'acide rétinoique au cours de la morphogenèse cutanée et dans les métaplasies induites par les rétinoides“. Université Joseph Fourier (Grenoble), 1997. http://www.theses.fr/1997GRE10172.
Der volle Inhalt der QuelleMatt, Nicolas. „Etude de la voie de signalisation de l'acide rétonoïque au cours du développement embryonnaire chez la souris : Approches génétiques et pharmacologiques“. Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13199.
Der volle Inhalt der QuelleGagné, David. „Influence de l'altération des isoformes des récepteurs de l'acide rétinoïque [bêta] sur l'expression des gènes Hox et leur implication possible dans la tumorigénèse pulmonaire et l'homéostasie du surfactant pulmonaire“. Mémoire, Université de Sherbrooke, 2001. http://savoirs.usherbrooke.ca/handle/11143/3268.
Der volle Inhalt der QuelleGutierrez, Mazariegos Juliana. „Evolution of the retinoic acid receptor“. Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0886.
Der volle Inhalt der QuelleRetinoic acid (RA) is a fat-soluble morphogen derived from vitamin A that controls key cellular and developmental processes in chordates. In vertebrates, the major actors of the RA signaling pathway are the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). The evolution of RAR is still poorly understood, however, recently RARs have been identified in the genome of non-chordate species, suggesting that RAR and the RA pathway might have a more ancient evolutionary origin than previously thought. The work presented in this manuscript allowed us to retrace the evolutionary history of RAR from its origin in Urbilateria to its diversification following whole genome duplication events in vertebrates. We describe the characterization of the RARs from an annelid, a mollusk and a sea urchin. We showed that the receptors from the annelid and the sea urchin are functional RARs, however, the receptor from the mollusk is not functional with RA. Studies carried out in the annelid revealed that the signaling pathways regulated by RA in this species are different to the ones it regulates in vertebrates. These observations raise questions about the function of RA and RAR on the embryonic development of non-chordate species and their possible function in Urbilateria. Finally, the molecular characterization of cyclostome RARs allowed us to characterize the impact of whole genome duplications on the evolution of the ligand-binding pocket. Altogether, these data will allow us to better understand the relationship between the receptor and its ligand and to reveal novel insights on the function of RAR in response to non-classical ligands
Viallet, Jean. „Modification homéotique de la morphogenèse cutanée chez l'embryon de souris et distribution des transcrits des gènes des récepteurs nucléaires de l'acide rétinoique et de deux classes de gènes à homéoboîte“. Grenoble 1, 1994. http://www.theses.fr/1994GRE10048.
Der volle Inhalt der QuelleTeletin, Marius. „Modèles murins de cancer du foie et de la prostate par invalidation de TIF1A (Transcription intermediary factor 1 alpha) et de PTEN (Phosphatase and tensin homolog), respectivement“. Université Louis Pasteur (Strasbourg) (1971-2008), 2007. http://www.theses.fr/2007STR13083.
Der volle Inhalt der QuelleCras, Audrey. „Résistance des cellules tumorales aux rétinoïdes : paramètres moléculaires prédictifs d'une réponse thérapeutique aux rexinoïdes et aux drogues épigénétiques“. Paris 7, 2009. http://www.theses.fr/2009PA077087.
Der volle Inhalt der QuelleRetinoids are involved in the regulation of key biological processes such as cell growth, differentiation and apoptosis. The effects of retinoic acid are mediated through nuclear receptors - retinoic acid receptors (RAR) and retinoid X receptors (RXR) - which act as ligand-dependent transcription factors. Despite the success of retinoic acid all-trans (ATRA) as differentiating agent in acute promyelocytic leukemia, the clinical use of retinoid remains limited. In this work, we studied retinoid actions in retinoid-resistant tumors cellular models, differentiated thyroid cancers and acute myeloid leukemia. Our results highlight the importance of RAR and RXR expression profile, and their induction in the retinoid sensitivity of cells. Bexarotene, a RXR agonist, inhibits cell growth and invasion ability of tumor cells resistant to ATRA by transcriptional repression of NF-kB signaling pathway. In addition, retinoid résistance is associated with lack of functionality of RAR transcriptional complex by epigenetic modifications. However, combination of ATRA with molecules modifying chromatin structure removes the transcriptional repression and induces the expression of RAR in ATRA-resistant cells. DMA methylation pattern analysis confirms that epigenetic modulation may be linked to drug efficacy. This work has enabled us, first, to define molecular parameters predictive of retinoid response, and secondly to identify therapeutic ways to bypass resistance and/or to restore ATRA sensitivity
Commere, Oustric Julie. „Apports nutritionnels en acides gras polyinsaturés n-3 et action cellulaire de la vitamine A : effets sur la plasticité cérébrale et la mémoire spatiale chez le rat agé“. Thesis, Bordeaux 1, 2010. http://www.theses.fr/2010BOR14211/document.
Der volle Inhalt der QuelleLong chain polyunsaturated fatty acids (LC-PUFA) of the n-3 series play essential roles in brain functions, including brain plasticity and memory processes which are altered during aging. It is now well accepted that these PUFA regulate gene transcription through binding and activating specific nuclear receptors such as PPAR (peroxisome proliferator-activated receptors) and RXR (retinoid X receptors, which also bind 9-cis retinoic acid). As a common heterodimeric partner of both PPAR and RAR (all-trans retinoic acid receptors), RXR is a key factor in the modulation of gene expression by fatty acids and retinoids. In this context, the purpose of this work was to study the effects of a n-3 LC-PUFA supplementation on fatty acid and retinoid signalling pathways and on cerebral plasticity and spatial memory processes. Our main results show that n-3 LC-PUFA supplementation for 21 weeks in mid-life rats, maintains the mRNA levels of RXRγ and GAP-43 (synaptic protein) which were altered in aged rat hippocampus. Besides, supplemented aged rats exhibited increased numbers of newly generated neurons and improved spatial working memory, when compared with control aged rats. To summarize, our results support the neuroprotective effects of n-3 LC-PUFA during aging, in particular on cerebral plasticity and working memory. Furthermore, our works suggest the implication of RXR in the set up of these effects through notably the regulation of some target genes involved in synaptic plasticity and hippocampal neurogenesis processes
Bellutti, Laura. „Régulation transcriptionnelle et entrée en méiose“. Thesis, Université de Paris (2019-....), 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=4244&f=28602.
Der volle Inhalt der QuelleMeiosis is a conserved process, allowing the production of haploid germ cells. In mammals, entry into meiosis is sexually dichotomic, taking place during fetal life in ovaries and during postnatal life in testes. In fetal ovaries, Retinoic Acid (RA) is believed to activate Stra8 (Stimulated by the retinoic acid gene 8), a key factor of mitosis/meiosis transition. In fetal testes, CYP26B1, a RA-metabolising enzyme, prevents Stra8 expression. However, the exact role of endogenous RA remains uncertain.The first objective of my work was to clarify the function of endogenous RA in meiotic initiation. For this purpose, we created a model of artificial RA deficiency by ex vivo electroporation of fetal gonads with plasmids encoding Cyp26b1 or Cyp26a1, two RA-metabolising enzymes. We observed that ectopic CYP26B1 is sufficient to prevent STRA8 appearance in germ cells from fetal ovaries. In contrast, overexpression of CYP26A1 only mildly affects the expression of Stra8 mRNA. We thus conclude that CYP26B1 acts independently of RA signalling pathway on meiotic initiation. We propose a two-step model with first a RA-independent Stra8 induction, followed by its RA-dependent amplification.Recently, MEIOC and YTHDC2 have been caracterised as key post-transcriptional regulators of mitosis/meiosis transition. Here, we compare the phenotypes of Stra8, Meioc and Ythdc2 mutant mice Their high similarity prompt us to hypothesise a continuity between transcriptional and post-transcriptional regulations. In parallel, we show that double invalidation of Stra8 and Meioc does not completely prevent meiotic initiation. Thus, we hypothesise the existence of other unknown mitosis/meiosis regulators.Finally, we characterised a genome wide arrest of transcription taking place during mitosis/meiosis transition. This transcriptional silencing is partly dependent of Stra8 but is independent of other key events of meiotic prophase I: double-strand breaks, homologous chromosome synapsis, axe-loop chromosome structure. We took advantage of a spermatogenesis synchronisation protocol and nascent RNA immunoprecipitation, to characterise the transcriptional landscape of early-meiotic germ cells. This highlighted stabilization and destabilization phemomena taking place during prophase I. As a whole, we show the high complexity level of meiosis initiation, which has to be finely regulated by the orchestration of transcriptional and post-transcriptional events
El, hajj Joelle. „Régulation de la télomérase dans un modèle de leucémie aigue promyélocytaire : rôle de l'ARN long non codant H19“. Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS123.
Der volle Inhalt der QuelleThe telomere / telomerase pair appears to be a promising target for potential anticancer agents that would be active on a wide range of tumors. The host laboratory has shown in a model of acute promyelocytic leukemia (APL), that a clinically used agent, retinoic acid (ATRA), exerts anti-tumor activity by repressing the transcription of the catalytic subunit hTERT regardless of differentiation. This model (NB4) with its resistant cell variants (NB4-LR1SFD) or not to the repression of hTERT (NB4-LR1) by ATRA is a tool of choice for the identification of hTERT regulatory factors and the search for molecular bases of its reactivation.A "microarray" approach has been used to identify new ATRA-mediated genes and / or signaling networks and potential hTERT regulators. Bioinformatic analysis allowed us to build differential expression profiles between the 2 lineages and interaction networks. Among the candidates, H19, a 2.5Kb long, polyadenylated and non-coding RNA. H19 is classified as a tumor suppressor gene: in its absence there is cancer development (case of Wilms tumor, embryonic rhabdomyosarcoma, Beckwith-Wiedman syndrome); its reintroduction by transfection leads to a loss of tumorigenicity. However H19 is increasingly recognized as an oncogene as its expression is elevated in several types of solid cancers. However, few studies are interested in the role of H19 in leukemias, hence our interest in studying it in the APL model that we have developed.We developed the H19 expression measurement by quantitative RT-PCR, validated the data obtained in the "microarray" analysis and showed that the ATRA treatment induces the expression of H19 in NB4-LR1 cells whereas this expression is rather diminished in NB4-LR1SFD cells. The induction observed in NB4-LR1 cells exists independently of differentiation. On the other hand, this induction can be observed associated with the differentiation or apoptosis in the NB4-LR1SFD cell line in parallel with a significant decrease in the expression of hTERT. This important result shows that the NB4-LR1SFD line does not have a general H19 induction defect. These data suggest the existence of an inverse correlation between the expression level of hTERT and that of H19 in this cellular model. Importantly, the analysis of publicly accessible APL patients’ databases finds this inverse correlation as well.We observed a decrease in telomerase activity in cellular extracts incubated in the presence of in vitro transcribed H19 RNA. This decrease in activity was also observed after overexpression of H19 in cellulo. The RIP (RNA immunoprecipitation) experiments showed a decrease in hTR amount bound to hTERT following an increase in H19 expression after ATRA treatment in vitro or after overexpression of H19 in cellulo. We hypothesize that H19 induces a displacement of hTR from the hTR-hTERT complex. However, the "pull-down" experiments failed to confirm the hypothesis of a possible interaction between H19 RNA and TERT protein.My thesis work identifies, for the first time, the long non-coding RNA H19, as a potential regulator of hTERT that can modify its activity. This work would propose not only a new mechanism of regulation of telomerase activity but also a new function for H19 in this type of cancer
Grenier, Émilie. „Modulation de la différenciation cellulaire, des apolipoprotéines et des lipoprotéines par l'acide rétinoïque“. Thèse, 2007. http://hdl.handle.net/1866/18208.
Der volle Inhalt der QuelleDumouchel, Annie. „Étude du rôle de l'acide rétinoïque dans le développement de la prostate“. Thèse, 2005. http://hdl.handle.net/1866/15557.
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