Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Ubiquitination and filamentous structure of cytidine triphosphate synthase. 2711 91

CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of filaments and mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS forms filaments in response to histidine influx during glutamine starvation. Tetramer conformation-based filament formation restricts CTPS enzymatic activity during nutrient deprivation. CTPS protein levels remain stable in the presence of histidine during nutrient deprivation, followed by rapid cell growth after stress relief. We demonstrate that filament formation is controlled by methylation and that histidine promotes re-methylation of homocysteine by donating one-carbon intermediates to the cytosolic folate cycle. Furthermore, we find that starvation stress and glutamine deficiency activate the GCN2/ATF4/MTHFD2 axis, which coordinates CTPS filament formation. CTPS filament formation induced by histidine-mediated methylation may be a strategy used by cancer cells to maintain homeostasis and ensure a growth advantage in adverse environments.
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PMID:Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase. 3018 6

CTP synthase (CTPS) cytoophidia have been found in many species over domains of life in the past 10 years, implying the evolutionary conservation of these structures. However, there are differences in cytoophidia between species. The difference in CTPS cytoophidium properties between budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) inspires this research. We studied the effects of culture environment on cytoophidia in S. cerevisiae by switching to the optimal medium for S. pombe. S. cerevisiae CTPS cytoophidium fragmentation and pseudohyphae formation were observed after treatment with S. pombe medium YES instead of S. cerevisiae medium YPD. By modifying the level of each ingredient of the media, we found that hypoosmolality impedes cytoophidium integrity during nitrogen starvation. Our study demonstrates the relationship between cytoophidium integrity and environmental stress, supporting the role of cytoophidia in stress resistance.
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PMID:Hypoosmolality impedes cytoophidium integrity during nitrogen starvation. 3329 93