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Le travail est divisé en deux parties.
1. Etude des isoformes longues et courtes de l’isoenzyme M
Ainsi qu’il est décrit plus haut, 2 isoformes de l’isoenzyme M peuvent exister puisque le cDNA correspondant possède 2 sites d’initiation pour la traduction. La première partie du travail sera consavrée à la purification de ces deux isoformes recombinantes surexprimées dans E. coli, ainsi qu’à la caractérisation de leurs propriétés cinétiques. En comparant ces données avec celles obtenues avec de la PFK-2/FBPase-2 purifiée à partir de muscle de rat on espère pouvoir déterminer quelle isoforme est exprimée dans le muscle.
2. Etude des propriétés des mutants Asp-152-Ala et Clu-157-Ala
La deuxième partie sera consacrée à l’étude de mutations effectuées dans le site actif de la PFK-2. D’après la similitude entre le site actif de la PFK-1 d’E. Coli et celui de la PFK-2/FBPase-2 de rat.
E. Coli PFK1 (122) Leu Pro Gly Thr Ile Asp Asn Asp Ile (130)
Foie PFK2 (155- Phe Ile Glu Ser Ile Cys Asn Asp Pro (163)
nous constatons que Asp-162 et Glu-157 pourraient être importants dans la catalyse en agissant comme Asp-127 de la PFK-1 d’E. Coli c’est –à-dire en ayant un rôle de catalyse basique. Asp-162 et Glu-157 ont été mutés en Ala et les propriétés des mutants ont été étudiées. Si ces résidus sont essentiels à la catalyse on s’attend à trouver une perte quasi complète de l’activité PFK-2 dans les mutants.
Le travail de ce mémoire consistera donc à purifier ces différents isoenzymes et à en caractériser les propriétés cinétiques afin de proposer une relation structure/activité de la PFK-2/FBPase-2

Phosphofructokinase-2 --- Fructose-Biphosphatase --- Mutation --- Medical Laboratory Science

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Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. An increasing amount of experimental and epidemiological evidence has been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors, etc.) may be implicated in either the promotion of or the protection against carcinogenesis. At the cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. Since there is a growing interest in the study of the biochemical and molecular role played by food components and its impact on cellular processes and/or gene expressions directed towards the fine-tuning of cancer phenotypes, in this Special Issue researchers contributed with either research or review articles presenting the latest findings on the intracellular pathways and mechanisms affected by natural bioactive dietary molecules.

Research & information: general --- Biology, life sciences --- berberine --- signaling pathways --- oncogenic cascades --- TRAIL --- microRNAs --- cancer therapy --- colon cancer cells --- ethanol --- Nrf2 --- HO-1 --- ER stress --- autophagy --- MMPs --- formononetin --- cancer --- preclinical models --- cell signaling --- angiogenesis --- nobiletin --- colorectal cancer --- chemoprevention --- bioactivities --- experimental therapeutics --- HDAC --- multiple myeloma --- oleacein --- breast cancer --- persistent organic pollutants --- breast cancer risk --- breast cancer prognostic --- systematic review --- carrageenan --- invasion --- metastasis --- RacGAP1 --- radiotherapy --- marine sponge --- natural product --- anticancer drug --- oral cancer inhibition --- phytochemicals --- small organic agents --- Piper eriopodon, alkenylphenols --- human cancer cells --- cell death --- apoptosis --- caspase-independent cell death --- XIAP antagonists --- XIAP-BIR3 domain --- Calocedrus formosana --- lung cancer --- yatein --- cell-cycle arrest --- xenograft --- isorhamnetin --- G2/M arrest --- ROS --- AMPK --- pancreatic cancer --- epigallocatechin-3-gallate (EGCG) --- gemcitabine --- glycolysis --- phosphofructokinase --- natural polyphenols --- anticancer activities --- molecular mechanisms --- Streptomyces --- mangrove --- anti-proliferative --- colon cancer --- epithelial mesenchymal transition --- inflammation --- malignant cancer --- natural anti-inflammatory compounds --- pro-resolving lipids --- anticancer drugs --- flavonoids --- natural compounds --- Xenopus laevis --- AOM/DSS model --- melanoma cells --- nicotine --- α9-nAChR --- PD-L1 --- STAT3 --- gigantol --- AKT --- JAK/STAT --- cancer stem cell --- tumor maintenance --- tumor density --- proteomics --- honokiol --- anticancer --- mechanism --- signalling pathway --- uterine sarcoma --- fucoidan --- isobolography --- colchicine alkaloid --- mesoporous silica nanoparticles --- targeted delivery system --- PD-1 immune checkpoint inhibitor and cancer immunotherapy --- glucose transport --- drugs --- innate immunity --- β-glucans --- nutrition --- immunotherapy --- estrogen --- estrogen receptor alpha --- polyphenols --- daidzein --- daidzein metabolites --- paclitaxel --- breast cancer cells --- obesity --- renin–angiotensin system --- eicosapentaenoic acid --- adipocyte inflammation --- olive leaf extract --- oleuropein --- Seahorse analysis --- cancer metabolism --- glycolytic markers --- Malva pseudolavatera Webb &amp --- Berthel. --- acute myeloid leukemia --- reactive oxygen species --- brain cancer --- gliomas --- schwannomas --- malignant tumors of the peripheral nerve sheath (MPNST) --- neurofibromas --- bioavailability --- nanoparticle-based delivery systems --- natural bioactive compound --- gallic acid --- EGFR signaling --- p53 --- EGCG --- non-coding RNAs --- anti-cancer drug --- NSCLC --- EGFR TKI --- FASN inhibitors --- resistance --- n/a --- renin-angiotensin system

Choose an application

• Reference Manager
• EndNote
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Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. An increasing amount of experimental and epidemiological evidence has been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors, etc.) may be implicated in either the promotion of or the protection against carcinogenesis. At the cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. Since there is a growing interest in the study of the biochemical and molecular role played by food components and its impact on cellular processes and/or gene expressions directed towards the fine-tuning of cancer phenotypes, in this Special Issue researchers contributed with either research or review articles presenting the latest findings on the intracellular pathways and mechanisms affected by natural bioactive dietary molecules.

berberine --- signaling pathways --- oncogenic cascades --- TRAIL --- microRNAs --- cancer therapy --- colon cancer cells --- ethanol --- Nrf2 --- HO-1 --- ER stress --- autophagy --- MMPs --- formononetin --- cancer --- preclinical models --- cell signaling --- angiogenesis --- nobiletin --- colorectal cancer --- chemoprevention --- bioactivities --- experimental therapeutics --- HDAC --- multiple myeloma --- oleacein --- breast cancer --- persistent organic pollutants --- breast cancer risk --- breast cancer prognostic --- systematic review --- carrageenan --- invasion --- metastasis --- RacGAP1 --- radiotherapy --- marine sponge --- natural product --- anticancer drug --- oral cancer inhibition --- phytochemicals --- small organic agents --- Piper eriopodon, alkenylphenols --- human cancer cells --- cell death --- apoptosis --- caspase-independent cell death --- XIAP antagonists --- XIAP-BIR3 domain --- Calocedrus formosana --- lung cancer --- yatein --- cell-cycle arrest --- xenograft --- isorhamnetin --- G2/M arrest --- ROS --- AMPK --- pancreatic cancer --- epigallocatechin-3-gallate (EGCG) --- gemcitabine --- glycolysis --- phosphofructokinase --- natural polyphenols --- anticancer activities --- molecular mechanisms --- Streptomyces --- mangrove --- anti-proliferative --- colon cancer --- epithelial mesenchymal transition --- inflammation --- malignant cancer --- natural anti-inflammatory compounds --- pro-resolving lipids --- anticancer drugs --- flavonoids --- natural compounds --- Xenopus laevis --- AOM/DSS model --- melanoma cells --- nicotine --- α9-nAChR --- PD-L1 --- STAT3 --- gigantol --- AKT --- JAK/STAT --- cancer stem cell --- tumor maintenance --- tumor density --- proteomics --- honokiol --- anticancer --- mechanism --- signalling pathway --- uterine sarcoma --- fucoidan --- isobolography --- colchicine alkaloid --- mesoporous silica nanoparticles --- targeted delivery system --- PD-1 immune checkpoint inhibitor and cancer immunotherapy --- glucose transport --- drugs --- innate immunity --- β-glucans --- nutrition --- immunotherapy --- estrogen --- estrogen receptor alpha --- polyphenols --- daidzein --- daidzein metabolites --- paclitaxel --- breast cancer cells --- obesity --- renin–angiotensin system --- eicosapentaenoic acid --- adipocyte inflammation --- olive leaf extract --- oleuropein --- Seahorse analysis --- cancer metabolism --- glycolytic markers --- Malva pseudolavatera Webb &amp --- Berthel. --- acute myeloid leukemia --- reactive oxygen species --- brain cancer --- gliomas --- schwannomas --- malignant tumors of the peripheral nerve sheath (MPNST) --- neurofibromas --- bioavailability --- nanoparticle-based delivery systems --- natural bioactive compound --- gallic acid --- EGFR signaling --- p53 --- EGCG --- non-coding RNAs --- anti-cancer drug --- NSCLC --- EGFR TKI --- FASN inhibitors --- resistance --- n/a --- renin-angiotensin system