The Experts below are selected from a list of 87 Experts worldwide ranked by ideXlab platform
Archan Chakraborty - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination and filamentous structure of Cytidine Triphosphate Synthase
Fly, 2016Co-Authors: Peiyu Wang, Archan ChakrabortyAbstract:ABSTRACTLiving organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, Cytidine-5′-Triphosphate (CTP) Synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP Synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP Synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP Synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubi...
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ubiquitination and filamentous structure of Cytidine Triphosphate Synthase
Fly, 2016Co-Authors: Limei Pai, Archan Chakraborty, Peiyu Wang, Wei Cheng Lin, Chau Ting Yeh, Yu Hung LinAbstract:Living organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, Cytidine-5'-Triphosphate (CTP) Synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP Synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP Synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP Synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubiquitination, as well as its physiological implications, in the regulation of CTP Synthase structure.
Peiyu Wang - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination and filamentous structure of Cytidine Triphosphate Synthase
Fly, 2016Co-Authors: Limei Pai, Archan Chakraborty, Peiyu Wang, Wei Cheng Lin, Chau Ting Yeh, Yu Hung LinAbstract:Living organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, Cytidine-5'-Triphosphate (CTP) Synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP Synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP Synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP Synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubiquitination, as well as its physiological implications, in the regulation of CTP Synthase structure.
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ubiquitination and filamentous structure of Cytidine Triphosphate Synthase
Fly, 2016Co-Authors: Peiyu Wang, Archan ChakrabortyAbstract:ABSTRACTLiving organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, Cytidine-5′-Triphosphate (CTP) Synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP Synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP Synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP Synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubi...
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filamentous structure of Cytidine Triphosphate Synthase
Applied Medical Informaticvs, 2015Co-Authors: Peiyu WangAbstract:Nucleotide biosynthesis is a highly regulated process essential for cell growth and replication. Cytidine Triphosphate Synthase (CTPsyn) is a metabolic enzyme that catalyzes the rate-limiting step of de novo CTP biosynthesis. In addition to being an essential nucleotide, CTP is a basic building molecule (or block) of RNA, DNA, and phospholipids. Recently, CTPsyn was independently revealed to have a filamentous structure in bacteria, budding yeast, Drosophila, and mammalian cell lines, indicating that its structure is highly evolutionarily conserved. In the present review, we briefly discuss recent findings and suggest that future studies investigating the biological effect of the polymeric structure of CTPsyn will be expected.
Jesse D Woodson - One of the best experts on this subject based on the ideXlab platform.
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chloroplast quality control pathways are dependent on plastid dna synthesis and nucleotides provided by Cytidine Triphosphate Synthase two
New Phytologist, 2021Co-Authors: Kamran Alamdari, Karen E Fisher, Snigdha Rai, Kyle Palos, Andrew D L Nelson, David W Tano, Jesse D WoodsonAbstract:Reactive oxygen species (ROS) produced in chloroplasts cause oxidative damage, but also signal to initiate chloroplast quality control pathways, cell death, and gene expression. The Arabidopsis thaliana plastid ferrochelatase two (fc2) mutant produces the ROS singlet oxygen in chloroplasts that activates such signaling pathways, but the mechanisms are largely unknown. Here we characterize one fc2 suppressor mutation and map it to Cytidine Triphosphate Synthase TWO (CTPS2), which encodes one of five enzymes in Arabidopsis necessary for de novo cytoplasmic CTP (and dCTP) synthesis. The ctps2 mutation reduces chloroplast transcripts and DNA content without similarly affecting mitochondria. Chloroplast nucleic acid content and singlet oxygen signaling are restored by exogenous feeding of the dCTP precursor deoxyCytidine, suggesting ctps2 blocks signaling by limiting nucleotides for chloroplast genome maintenance. An investigation of CTPS orthologs in Brassicaceae showed CTPS2 is a member of an ancient lineage distinct from CTPS3. Complementation studies confirmed this analysis; CTPS3 was unable to compensate for CTPS2 function in providing nucleotides for chloroplast DNA and signaling. Our studies link cytoplasmic nucleotide metabolism with chloroplast quality control pathways. Such a connection is achieved by a conserved clade of CTPS enzymes that provide nucleotides for chloroplast function, thereby allowing stress signaling to occur.
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chloroplast quality control pathways are dependent on plastid dna synthesis and nucleotides provided by Cytidine Triphosphate Synthase two
bioRxiv, 2020Co-Authors: Kamran Alamdari, Karen E Fisher, D W Welsh, Snigdha Rai, Kyle Palos, Andrew D L Nelson, Jesse D WoodsonAbstract:Summary Reactive oxygen species (ROS) produced in chloroplasts cause oxidative damage, but also signal to initiate chloroplast quality control pathways, cell death, and gene expression. The mechanisms behind these signals are largely unknown. The Arabidopsis thaliana plastid ferrochelatase two (fc2) mutant produces the ROS singlet oxygen in chloroplasts that activates such signaling pathways. Here we mapped one fc2 suppressor mutation to Cytidine Triphosphate Synthase TWO (CTPS2), which encodes one of five enzymes in Arabidopsis necessary for de novo cytoplasmic CTP (and dCTP) synthesis. The ctps2 mutation reduces chloroplast transcripts and DNA content without similarly affecting mitochondria. Chloroplast nucleic acid content and singlet oxygen signaling are restored by exogenous feeding of the dCTP precursor deoxyCytidine, suggesting ctps2 blocks signaling by limiting nucleotides for chloroplast genome maintenance. An investigation of CTPS orthologs in Brassicaceae showed CTPS2 is a member of an ancient lineage distinct from CTPS3. Complementation studies confirmed this analysis; CTPS3 was unable to compensate for CTPS2 function in providing nucleotides for chloroplast DNA and signaling. Our studies link cytoplasmic nucleotide metabolism with chloroplast quality control pathways. Such a connection is achieved by a conserved clade of CTPS enzymes that may have evolved specialized functions in providing nucleotides to specific subcellular compartments.
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Cytidine Triphosphate Synthase two provides nucleotides for chloroplast development and stress responses
bioRxiv, 2020Co-Authors: Kamran Alamdari, Karen E Fisher, D W Welsh, Snigdha Rai, Kyle Palos, Andrew D L Nelson, Jesse D WoodsonAbstract:O_LIReactive oxygen species (ROS) produced in chloroplasts cause oxidative damage, but also signal to control chloroplast quality control, cell death, and gene expression. The mechanisms behind these pathways remain largely unknown. C_LIO_LIThe Arabidopsis thaliana plastid ferrochelatase two (fc2) mutant produces the ROS singlet oxygen in chloroplasts that activates such signaling pathways. Here we mapped one fc2 suppressor mutation to Cytidine Triphosphate Synthase TWO (CTPS2), which encodes one of five enzymes in Arabidopsis necessary for cytoplasmic de novo CTP (and dCTP) synthesis. C_LIO_LIThe ctps2 mutation blocks singlet oxygen signals by specifically reducing plastid (not mitochondrial) transcripts and DNA content. These phenotypes are restored by exogenous feeding of the dCTP precursor deoxyCytidine, suggesting that ctps2 blocks signaling by limiting nucleotides for plastid genome maintenance. C_LIO_LIAn investigation of CTPS orthologs in Brassicaceae showed that CTPS2 is a member of an ancient lineage distinct from CTPS3. Complementation studies confirmed this analysis; CTPS3 was unable to compensate for CTPS2 function in providing nucleotides for plastid DNA and chloroplast signaling. C_LIO_LIOur studies link cytoplasmic nucleotide metabolism with chloroplast quality control pathways. Such a connection is achieved by CTPS enzymes that may have evolved specialized functions in providing nucleotides to specific subcellular compartments. C_LI
Barbara H Zimmermann - One of the best experts on this subject based on the ideXlab platform.
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a ctp Synthase undergoing stage specific spatial expression is essential for the survival of the intracellular parasite toxoplasma gondii
Frontiers in Cellular and Infection Microbiology, 2018Co-Authors: Heidy Y Narvaezortiz, Andrea J Lopez, Nishith Gupta, Barbara H ZimmermannAbstract:Cytidine Triphosphate Synthase catalyzes the synthesis of Cytidine 5'-Triphosphate (CTP) from uridine 5'-Triphosphate (UTP), the final step in the production of Cytidine nucleotides. CTP Synthases also form filamentous structures of different morphologies known as cytoophidia, whose functions in most organisms are unknown. Here, we identified and characterized a novel CTP Synthase (TgCTPS) from Toxoplasma gondii. We show that TgCTPS is capable of substituting for its counterparts in the otherwise lethal double mutant (ura7Δ ura8Δ) of Saccharomyces cerevisiae. Equally, recombinant TgCTPS purified from Escherichia coli encodes for a functional protein in enzyme assays. The epitope-tagged TgCTPS under the control of its endogenous promoter displays a punctate cytosolic distribution, which undergoes spatial reorganization to form foci or filament-like structures when the parasite switches from a nutrient-replete (intracellular) to a nutrient-scarce (extracellular) condition. An analogous phenotype is observed upon nutrient stress or after treatment with a glutamine analog, 6-diazo-5-oxo-L-norleucine (DON). The exposure of parasites to DON disrupts the lytic cycle, and the TgCTPS is refractory to a genetic deletion, suggesting an essential requirement of this enzyme for T. gondii. Not least, this study, together with previous studies, supports that CTP Synthase can serve as a potent drug target, because the parasite, unlike human host cells, cannot compensate for the lack of CTP Synthase activity.
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DataSheet1.pdf
2018Co-Authors: Heidy Y. Narvaez-ortiz, Andrea J Lopez, Nishith Gupta, Barbara H ZimmermannAbstract:Cytidine Triphosphate Synthase catalyzes the synthesis of Cytidine 5′-Triphosphate (CTP) from uridine 5′-Triphosphate (UTP), the final step in the production of Cytidine nucleotides. CTP Synthases also form filamentous structures of different morphologies known as cytoophidia, whose functions in most organisms are unknown. Here, we identified and characterized a novel CTP Synthase (TgCTPS) from Toxoplasma gondii. We show that TgCTPS is capable of substituting for its counterparts in the otherwise lethal double mutant (ura7Δ ura8Δ) of Saccharomyces cerevisiae. Equally, recombinant TgCTPS purified from Escherichia coli encodes for a functional protein in enzyme assays. The epitope-tagged TgCTPS under the control of its endogenous promoter displays a punctate cytosolic distribution, which undergoes spatial reorganization to form foci or filament-like structures when the parasite switches from a nutrient-replete (intracellular) to a nutrient-scarce (extracellular) condition. An analogous phenotype is observed upon nutrient stress or after treatment with a glutamine analog, 6-diazo-5-oxo-L-norleucine (DON). The exposure of parasites to DON disrupts the lytic cycle, and the TgCTPS is refractory to a genetic deletion, suggesting an essential requirement of this enzyme for T. gondii. Not least, this study, together with previous studies, supports that CTP Synthase can serve as a potent drug target, because the parasite, unlike human host cells, cannot compensate for the lack of CTP Synthase activity.
Yu Hung Lin - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination and filamentous structure of Cytidine Triphosphate Synthase
Fly, 2016Co-Authors: Limei Pai, Archan Chakraborty, Peiyu Wang, Wei Cheng Lin, Chau Ting Yeh, Yu Hung LinAbstract:Living organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, Cytidine-5'-Triphosphate (CTP) Synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP Synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP Synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP Synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubiquitination, as well as its physiological implications, in the regulation of CTP Synthase structure.
