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)

Nvj1p resides in the outer nuclear membrane (ONM) and binds the vacuole membrane protein Vac8p to form nucleus-vacuole (NV) junctions in Saccharomyces cerevisiae. The induction of NVJ1 expression during starvation results in the sequestration of two additional binding partners, Tsc13p and Osh1p. Here, we map the domains of Nvj1p responsible for ONM targeting and partner binding. ONM targeting requires both the N-terminal signal anchor-like sequence and the topogenic membrane-spanning domain of Nvj1p. The N-terminal signal anchor-like sequence may anchor Nvj1p in the ONM by bridging to the inner nuclear membrane. A region encompassing the membrane-spanning domain is sufficient to bind Tsc13p. Osh1p and Vac8p bind to distinct regions in the cytoplasmic tail of Nvj1p. Overexpression of Nvj1p in trp1 cells causes a growth defect in low tryptophan that is rescued by additional copies of TAT1 or TAT2 tryptophan permeases. Conversely, nvj1-Delta trp1 cells grow faster than NVJ1+ trp1 cells in limiting tryptophan. Importantly, deleting the Osh1p-binding domain of Nvj1p abrogates the tryptophan transport-related growth defect of Nvj1p-overexpressing cells. Therefore, the Nvj1p-dependent sequestration of Osh1p negatively regulates tryptophan uptake from the medium, possible by affecting the trafficking of tryptophan permeases to the plasma membrane.
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PMID:Structure and function of nucleus-vacuole junctions: outer-nuclear-membrane targeting of Nvj1p and a role in tryptophan uptake. 1691 77

Quinine is a major drug of choice for the treatment of malaria. However, the primary mode of quinine action is unclear, and its efficacy is marred by adverse reactions among patients. To help address these issues, a genome-wide screen for quinine sensitivity was carried out using the yeast deletion strain collection. Quinine-sensitive mutants identified in the screen included several that were defective for tryptophan biosynthesis (trp strains). This sensitivity was confirmed in independent assays and was suppressible with exogenous Trp, suggesting that quinine caused Trp starvation. Accordingly, quinine was found to inhibit [(3)H]Trp uptake by cells, and the quinine sensitivity of a trp1Delta mutant could be rescued by overexpression of Trp permeases, encoded by TAT1 and TAT2. The site of quinine action was identified specifically as the high affinity Trp/Tyr permease, Tat2p, with which quinine associated in a Trp-suppressible manner. A resultant action also on Tyr levels was reflected by the Tyr-suppressible quinine hypersensitivity of an aro7Delta deletion strain, which is auxotrophic for Tyr (and Phe). The present genome-wide dataset provides an important resource for discovering modes of quinine toxicity. That potential was validated with our demonstration that Trp and Tyr uptake via Tat2p is a major target of cellular quinine toxicity. The results also suggest that dietary tryptophan supplements could help to avert the toxic effects of quinine.
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PMID:The antimalarial drug quinine disrupts Tat2p-mediated tryptophan transport and causes tryptophan starvation. 1941 71

Plants produce various l-tyrosine (Tyr)-derived compounds that are critical for plant adaptation and have pharmaceutical or nutritional importance for human health. Tyrosine aminotransferases (TATs) catalyze the reversible reaction between Tyr and 4-hydroxyphenylpyruvate (HPP), representing the entry point in plants for both biosynthesis of various natural products and Tyr degradation in the recycling of energy and nutrients. To better understand the roles of TATs and how Tyr is metabolized in planta, here we characterized single and double loss-of-function mutants of TAT1 (At5g53970) and TAT2 (At5g36160) in the model plant Arabidopsis thaliana As reported previously, tat1 mutants exhibited elevated and decreased levels of Tyr and tocopherols, respectively. The tat2 mutation alone had no impact on Tyr and tocopherol levels, but a tat1 tat2 double mutant had increased Tyr accumulation and decreased tocopherol levels under high-light stress compared with the tat1 mutant. Relative to WT and the tat2 mutant, the tat1 mutant displayed increased vulnerability to continuous dark treatment, associated with an early drop in respiratory activity and sucrose depletion. During isotope-labeled Tyr feeding in the dark, we observed that the tat1 mutant exhibits much slower 13C incorporation into tocopherols, fumarate, and other tricarboxylic acid (TCA) cycle intermediates than WT and the tat2 mutant. These results indicate that TAT1 and TAT2 function together in tocopherol biosynthesis, with TAT2 having a lesser role, and that TAT1 plays the major role in Tyr degradation in planta Our study also highlights the importance of Tyr degradation under carbon starvation conditions during dark-induced senescence in plants.
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PMID:TAT1 and TAT2 tyrosine aminotransferases have both distinct and shared functions in tyrosine metabolism and degradation in Arabidopsis thaliana. 3063 Sep 53