Índice
Literatura académica sobre el tema "Inhibiteur p16 de kinase cycline-dépendante"
Crea una cita precisa en los estilos APA, MLA, Chicago, Harvard y otros
Consulte las listas temáticas de artículos, libros, tesis, actas de conferencias y otras fuentes académicas sobre el tema "Inhibiteur p16 de kinase cycline-dépendante".
Junto a cada fuente en la lista de referencias hay un botón "Agregar a la bibliografía". Pulsa este botón, y generaremos automáticamente la referencia bibliográfica para la obra elegida en el estilo de cita que necesites: APA, MLA, Harvard, Vancouver, Chicago, etc.
También puede descargar el texto completo de la publicación académica en formato pdf y leer en línea su resumen siempre que esté disponible en los metadatos.
Tesis sobre el tema "Inhibiteur p16 de kinase cycline-dépendante"
Gendre-Gilles, Laure. "Régulation de l'arrêt des endomitoses et de la différenciation mégacaryocytaire terminale : rôle de p19 INK4D et de MAL". Paris 7, 2009. http://www.theses.fr/2009PA077075.
Texto completoMegakaryopoiesis is the System of platelet production divided in three steps: mitosis step, increase in ploidy level by endomitosis, platelet sheeding by cytoplasm fragmentation. My work focused on megakaryopoiesis through the study of two proteins: MAL and p19INK4D (p19). MAL is a transcriptional co-activator of SRF. In acute megakaryoblastic leukemia, thé MAL gene is translocated and fused with the gene encoding OTT. We showed that MAL expression increases during the megakaryocyte (MK) differentiation. MAL knockdown in MK progenitors reduced the percentage of cells forming filopodia, lamellipodia and stress fibers, and reduced proplatelet formation. MAL repression led to dysmorphic MK with disorganized demarcation membranes and alpha granules heterogeneously scattered in the cytoplasm. Gene expression profiling revealed a decrease in MMP9 and MYL9 expression after MAL inhibition. Chromatin immunoprecipitation in MK showed that the MAL/SRF complex directly regulates MYL9 and MMP9. MK migration was considerably decreased after MAL knock down, implicating MMP9 in migration. Finally, the use of a shRNA to decrease MYL9 expression showed that MYL9 was involved in proplatelet formation. P19 expression was increased during ploidization. We showed that p19 knockdown led to an increase in the mean ploidy of human MKs. This increase in ploidy was associated with a decrease in the more mature MKpopulation. Inversely, p19 overexpression resulted in a decrease in mean ploidy level. Confirming these results, bone marrow MKs from p19 KO mice exhibited an increase in mean ploidy level. Finally we showed that p19 is directly regulated by the hematopoietic transcription factor AML1
Sampaio, Gonçalves Daniel. "Cellular senescence : a complex interplay between tumor suppression and embryonic signaling". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ040.
Texto completoCellular senescence is a state of permanent cell cycle arrest, mediated by tumor suppressor genes including CDKN2A. Senescent cells are also highly communicative through a secretory component known as the SASP. While a primary function of senescence is to protect from cancer, it also plays critical roles in embryonic development and tissue regeneration. Given the link between senescence, development, and regeneration, I performed bioinformatics analysis on different senescent cell models. I found evidence suggesting that senescence is accompanied by several developmental-related signatures. These were associated with an overexpression of genes implicated in embryonic development, many of which were shared by senescent cells isolated from the Apical ectodermal Ridge in the developing limb. In addition, prolonged SASP exposure induced developmental genes and signatures, concurrently activating many developmental transcription factors, and potential senescence mediators including Zkscan2, a potential regulator of CDKN2A. Altogether these findings imply that the senescence program involves a general reactivation of developmental processes
Eller, Carla. "Un criblage gain-de-fonction identifie CDKN2C comme facteur d'hôte impliqué dans le cycle viral du virus de l'hépatite B". Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ103.
Texto completoHepatitis B is caused by the hepatitis B virus (HBV) and is a major cause of progressive liver disease including cirrhosis and hepatocellular carcinoma (HCC), the second leading cause of cancer death worldwide. HBV infects human hepatocytes, and, because of the tiny size of its genome, depends on multiple host functions, contributing to species and tissue tropism. However, fundamental virus-host interactions remain obscure, owing to the lack of robust infectious models for HBV research. An innovative functional genomics screen revealed the role of CDKN2C as proviral host factor promoting HBV replication in a step of the life cycle after the formation of covalently closed circular (ccc) DNA via its function as cell cycle regulator. This provides a better understanding of virus-host interactions and limitations of currently available cell culture systems, and will contribute to the development of physiological infectious model systems and novel therapeutic strategies for viral cure
Eymin, Béatrice. "Relations entre cycle cellulaire et apoptose chimio-induite des cellules leucémiques humaines : le rôle du gène gadd153 et de la protéine p27kip1". Dijon, 1999. http://www.theses.fr/1999DIJOMU06.
Texto completoLefevre, Gaëlle. "Identification des voies de signalisation participant à la tumorigénèse du mélanome choroïdien humain : implications thérapeutiques". Paris 7, 2004. http://www.theses.fr/2004PA077232.
Texto completoUveal melanoma is the most frequent intraocular primary tumour in adults. Although this cancer has a low incidence, its aggressive character as well as the absence of current satisfactory therapeutics to treat it lead us to study its physiopathology. We compared the expression levels of 120 proteins in both normal and tumoral melanocytes. We found that the ERK pathway was deregulated. We further confirmed that this deregulation was a major trait in uveal melanoma cells and that it was important for both the proliferation and transformation of these cells. We also identified two alterations responsible for the overactivation of the ERK pathway: 1) the presence of mutant B-Rafv599E and 2) the existence of an autocrine loop of activation by SCF/c-Kit. Inhibition of this latter with STI571 demonstrated promising in vitro results for future therapeutic application
Baccini, Véronique. "Polyploïdisation des mégacaryocytes : Rôle de P21cip1 et P27kip1 et de la voie de signalisation mammalian Target of Rapamycin (mTOR)". Paris 7, 2007. http://www.theses.fr/2007PA077180.
Texto completoMegakaryocyte differentiation is characterized by polyploidization of progenitors and cell size increasing. The term of differentiation is controlled by thrombopoietin (TPO) which stimulates various types of intracellular signaling pathways. The aim of my thesis was to understand mechanisms responsible for polyploidization and megakaryocyte (MK) maturation. The Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors which include p21Cip1 , p27Kip1 and p57Kip2 plays a crucial role in coupling cell-cycle arrest with differentiation in many cell types. MKs express high levels of p21Cip1 and p27Kip1 during differentiation. We hypothesized that these proteins act redundantly to arrest endomitosis and to induce terminal differentiation. We showed that only p21Cip1 was probably responsible for the arrest of endomitotic cell cycles by studying megakaryocytopoiesis of mice lacking one or the two proteins and the effects of overexpression of these proteins on megakaryocytopoiesis. Nevertheless, this murine model is insufficient to affirm thé absence of functional redundance between p21Cip1 and p27Kip1 during MK differentiation. We next showed the mammalian Target Of Rapamycin (mTOR) stimulation by TPO in MKs. This cell signaling pathway regulates cell growth (cell mass and cell size) of many cell types by increasing G1 phase progression through the TORC1 complex. We studied the rapamycin effects on culture of primary MKs and showed that mTOR pathway regulates MK proliferation, ploidization and size by increasing cyclin D3 and p21Cip1 transcription. In addition, mTOR régulates proplatelet formation independently from its effects on ploidization and cell growth
Passaro, Diana. "Dissection of phenotypic traits and molecular mechanisms underlying Cn/NFAT pathway activation in T-ALL". Paris 7, 2013. http://www.theses.fr/2013PA077263.
Texto completoDespite their initial efficient response to induction chemotherapy, relapse remains frequent in patients with T-ALL. Previous results from the laboratory revealed that Cn is active and has a pro-oncogenic fonction in mouse models of human T-ALL. Using an ICN1-induced T-ALL mouse model, in which conditional Cn genetic deletion is restricted to leukemic cells, we demonstrated that Cn is intrinsically required for the ability of leukemic cells to propagate the disease (LIC activity). Importantly, combination of vincristine treatment with Cn inactivation cooperated to induce long-term remission of ICN1-induced T-ALL. Phenotypically, Cn deletion altered the functional interactions between leukemic cells and the supportive MS5 stromal cell line ex vivo, resulting in reduced leukemic cell survival, proliferation, migration and clonogenic potential. At the molecular level, transcriptomic analysis revealed that Cn deletion was associated with the deregulation of the expression of >400 genes. We analysed the consequences of Cdkn la (p21) up-regulation upon Cn deletion, showing that it likely participates to the cell cycle arrest observed in Cn-deficient leukemic cells. We also found that expression of Cxcr4 was down-regulated at the surface of leukemic cells upon Cn deletion, a mechanism that we found responsible of the decreased motility of Cn-deficient leukemic cells. Finally, using ICN1- induced T-ALL mouse m odel in which NFATc 1, NFATc2 and NFATc3 genes could be conditionally inactivated, we demonstrated a role for NFAT in the survival, proliferation, motility and LIC activity of leukemic cells
Hannou, Sarah Anissa. "Rôle du régulateur du cycle cellulaire p16INK4a dans le développement du diabète de type 2 et dans les maladies métaboliques du foie gras ou NAFLD (Non-Alcoholic Fatty Liver Disease) : rôle de p16INK4a dans le contrôle de la néoglucogenèse hépatique et dans le développement de la stéatose hépatique non alcoolique". Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S012/document.
Texto completoP16INK4a is a tumor suppressor protein well described as a cell cycle regulator. p16INK4a blocks cyclin D/ cyclin dependent kinase (CDK) 4 activity by binding to the catalytic subunit of CDK4, preventing retinoblastoma protein phosphorylation and subsequently the release of the E2F1 transcription factor. As a consequence; the transcription of genes required for progression to the S phase is restrained. Recently, genome-wide association studies (GWAS) associated the CDKN2A locus, encoding, amongst other genes, p16INK4A, with an increased risk of type 2 diabetes (T2D) development. However, the pathophysiological link between p16INK4a and hepatic glucose homeostasis remains unknown. In this context, we investigated the role of p16INK4a in hepatic glucose metabolism in vivo using p16+/+ and p16-/- mice and in vitro using primary hepatocytes and the AML12 hepatocyte cell line.p16-/- mice exhibited a higher response to fasting as shown by an increased hepatic gluconeogenic gene expression including phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-biphosphatase (F1,6P) and glucose-6-phosphatase (G6Pase). p16-/- mice displayed an enhanced hepatic gluconeogenic activity in vivo upon administration of pyruvate, a gluconeogenic substrate. Consistent with this, in vitro data show that p16-/- primary hepatocytes display an enhanced gluconeogenic response to glucagon. In addition, knock down of p16INK4a by siRNA in AML12 cells increased gluconeogenic gene expression. These effects were associated with an increased activity of the PKA-CREB signaling pathway which leads to increased PPARg coactivator 1 (PGC1)α expression, a key transcriptional co-activator that regulates genes involved in energy metabolism. These findings describe a new function for p16INK4a as an actor in the hepatic adaptation to metabolic stress and suggest that p16INK4a could play a role during T2D development
Bendjeddou, Lyamin. "Synthèse et évaluation biologique de nouveaux inhibiteurs de kinases : identification d‘inhibiteurs de kinases parasitaires". Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P615.
Texto completoPhosphorylation by protein kinases is one of the most important post-translational modification in cellular processes such as division, differentiation, proliferation and apoptosis. Kinase deregulation is associated with numerous diseases such as cancer or neurodegenerative diseases. Imidazo[1,2-b]pyridazine and imidazo[4,5-b]pyridine were prepared to inhibit protein kinases involved in diseases targeted in the laboratory. The imidazo[1,2-b]pyridazines were synthesized to identify inhibitors of CLK1 and DYRK1A, potential targets in Alzheimer's disease. Among the imidazo[1,2-b]pyridazines synthesized, several molecules were found selective of DYRKs and CLKs, with IC50 < 100 nM. A structure-activity relationship based on the synthesis of 70 molecules, led to the identification of the structural bases of the selectivity. Products were also evaluated against parasite kinases. It was possible to identify some highly potent inhibitors on PfCLK1. The aim of second part of this thesis was to optimize the synthetic process to obtain imidazo[4,5-b]pyridines, which are close analogues of roscovitine. Derivatives had proved capable of inhibiting the formation of cysts in a cellular model of polycystic kidney disease. A seven-step synthesis has led to several grams of 3,5,7-trisubstituted imidazo[4,5-b]pyridine which is now available for evaluation in vivo