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The purinosome - a multi-protein complex involved in the de novo purine synthesis
Kráčmarová, Markéta ; Zikánová, Marie (advisor) ; Hálová, Martina (referee)
The purinosome is a multiprotein complex involved in the de novo purine synthesis (DNPS). Through a several steps of this metabolic pathway 5-phosphoribosyl-1- pyrophosphate is converted to inosinmonophosphate which is the precursor of purine nucleotides. Purine nucleotides are also synthesized from inosinmonophosphate through a salvage pathway that utilizes hypoxanthine. The purinosome is a dynamic multienzyme complex which is assembled and diassembled by actual need and availability of purines. The purinosome assembly is disrupted particularlly in the inherited disorders of the DNPS enzymes - AICA-ribosiduria and adenylosuccinate lyase deficiency (dADSL). Detailed studies of assembly and dynamics of purinosome and identification of molecular changes associated with the formation of purinosome under physiological and pathological conditions are object of research. Besides better understanding of purine metabolism in the future it could open up new possibilities of drug development especially of chemotherapeutics that block DNPS. Key words: purinosome, de novo purine synthesis, defects of enzymes, metabolism, purinosome interactions, cell control
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The purinosome - a multi-protein complex involved in the de novo purine synthesis
Kráčmarová, Markéta ; Zikánová, Marie (advisor) ; Macůrková, Marie (referee)
The purinosome is a multiprotein complex involved in the de novo purine synthesis (DNPS). Through a several steps of this metabolic pathway 5-phosphoribosyl-1-pyrophosphate is converted to inosine monophosphate, the precursor of purine nucleotides. Purine nucleotides are also synthesized from inosine monophosphate via a salvage pathway that utilizes hypoxanthine. The purinosome is a dynamic multienzyme complex which is assembled and diassembled by actual need and availability of purines. The purinosome assembly is disrupted in the inherited disorders of the DNPS enzymes - AICA- ribosiduria and adenylosuccinate lyase deficiency. Detailed studies of assembly and dynamics of purinosome and identification of molecular changes associated with the formation of purinosome under physiological and pathological conditions are object of research. Besides better understanding of purine metabolism, in the future, it can open up new possibilities of drug development especially of new use of chemotherapeutics that block DNPS. Key words: purinosome, de novo purine synthesis, defects of enzymes, metabolism, purinosome interactions, cell control
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Analysis of the intracellular localization of nucleophosmin: effect of C-terminal mutations
Kráčmarová, Markéta ; Brodská, Barbora (advisor) ; Čáp, Michal (referee)
C-terminal mutations of the phosphoprotein nucleophosmin (NPM) are the most frequent genetic aberration detected in adult acute myeloid leukemia (AML). I focused on characterization of type A, B and E of AML-related C-terminal mutations. The plasmids bearing fluorescently labeled wild type or mutated NPM have been constructed to characterize mutation-induced changes in the localization of NPM. Mammalian cell lines HEK293T, HeLa and NIH 3T3 were used for production of the chimeric proteins. The intracellular localization of the mutated forms of NPM was analyzed by immunofluorescence staining and fluorescence microscopy of the living cells. The localization of the mutNPM type A and B was almost identical and predominantly cytoplasmic, while mutNPM type E was detected in nucleolus and cytoplasm simultaneously. However localization of the mutated forms was greatly influenced by the used cell line. It has been demonstrated that the exogenous NPM interacts with the endogenous NPM and that they mutually affect their intracellular localization due to heterooligomer formation. Detailed analysis of the relationship between the C-terminal mutations and the localization of the mutated NPM improves understanding of specific mutation effect on the formation and progression of AML and also specifies its prognostic...
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The purinosome - a multi-protein complex involved in the de novo purine synthesis
Kráčmarová, Markéta ; Zikánová, Marie (advisor) ; Hálová, Martina (referee)
The purinosome is a multiprotein complex involved in the de novo purine synthesis (DNPS). Through a several steps of this metabolic pathway 5-phosphoribosyl-1- pyrophosphate is converted to inosinmonophosphate which is the precursor of purine nucleotides. Purine nucleotides are also synthesized from inosinmonophosphate through a salvage pathway that utilizes hypoxanthine. The purinosome is a dynamic multienzyme complex which is assembled and diassembled by actual need and availability of purines. The purinosome assembly is disrupted particularlly in the inherited disorders of the DNPS enzymes - AICA-ribosiduria and adenylosuccinate lyase deficiency (dADSL). Detailed studies of assembly and dynamics of purinosome and identification of molecular changes associated with the formation of purinosome under physiological and pathological conditions are object of research. Besides better understanding of purine metabolism in the future it could open up new possibilities of drug development especially of chemotherapeutics that block DNPS. Key words: purinosome, de novo purine synthesis, defects of enzymes, metabolism, purinosome interactions, cell control
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The purinosome - a multi-protein complex involved in the de novo purine synthesis
Kráčmarová, Markéta ; Zikánová, Marie (advisor) ; Macůrková, Marie (referee)
The purinosome is a multiprotein complex involved in the de novo purine synthesis (DNPS). Through a several steps of this metabolic pathway 5-phosphoribosyl-1-pyrophosphate is converted to inosine monophosphate, the precursor of purine nucleotides. Purine nucleotides are also synthesized from inosine monophosphate via a salvage pathway that utilizes hypoxanthine. The purinosome is a dynamic multienzyme complex which is assembled and diassembled by actual need and availability of purines. The purinosome assembly is disrupted in the inherited disorders of the DNPS enzymes - AICA- ribosiduria and adenylosuccinate lyase deficiency. Detailed studies of assembly and dynamics of purinosome and identification of molecular changes associated with the formation of purinosome under physiological and pathological conditions are object of research. Besides better understanding of purine metabolism, in the future, it can open up new possibilities of drug development especially of new use of chemotherapeutics that block DNPS. Key words: purinosome, de novo purine synthesis, defects of enzymes, metabolism, purinosome interactions, cell control
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