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https://www.readbyqxmd.com/read/28810702/the-nutrient-transceptor-pka-pathway-functions-independently-of-tor-and-responds-to-leucine-and-gcn2-in-a-tor-independent-manner
#1
Michaela Conrad, Harish Nag Kankipati, Marlies Kimpe, Griet Van Zeebroeck, Zhiqiang Zhang, Johan M Thevelein
Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline...
August 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28804003/effect-and-proposed-mechanism-of-vitamin-c-modulating-amino-acid-regulation-of-autophagic-proteolysis
#2
Md Razaul Karim, Motoni Kadowaki
Autophagy is an intracellular bulk degradation process, induced under nutrient starvation. Failure of autophagy has been recognized as a contributor to aging and multiple age related neurodegenerative diseases. Improving autophagy is a beneficial anti-aging strategy, however very few physiological regulators have been identified. Here, we demonstrate that vitamin C is a nutritional stimulator of autophagy. Supplementation of fresh hepatocytes with vitamin C increased autophagic proteolysis significantly in the presence of amino acids in a dose- and time-dependent manner, although no effect was observed in the absence of amino acids...
August 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28771613/activation-of-gcn2-in-response-to-different-stresses
#3
Silje Anda, Róbert Zach, Beáta Grallert
All organisms have evolved pathways to respond to different forms of cellular stress. The Gcn2 kinase is best known as a regulator of translation initiation in response to starvation for amino acids. Work in budding yeast has showed that the molecular mechanism of GCN2 activation involves the binding of uncharged tRNAs, which results in a conformational change and GCN2 activation. This pathway requires GCN1, which ensures delivery of the uncharged tRNA onto GCN2. However, Gcn2 is activated by a number of other stresses which do not obviously involve accumulation of uncharged tRNAs, raising the question how Gcn2 is activated under these conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28767134/the-differential-impact-of-amino-acids-on-oxphos-system-activity-following-carbohydrate-starvation-in-arabidopsis-cell-suspensions
#4
João Henrique F Cavalcanti, Carla G S Quinhones, Peter Schertl, Danielle S Brito, Holger Eubel, Tatjana Hildebrandt, Adriano Nunes-Nesi, Hans-Peter Braun, Wagner L Araújo
Plant respiration mostly depends on the activity of glycolysis and the oxidation of organic acids in the tricarboxylic acid (TCA) cycle to synthesize ATP. However, during stress situations plant cells also use amino acids as alternative substrates to donate electrons via the ETF/ETFQO complex to the mitochondrial electron transport chain (mETC). Given to this, here we investigated changes of the oxidative phosphorylation (OXPHOS) system in Arabidopsis thaliana cell culture under carbohydrate starvation supplied with a range of amino acids...
August 2, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28765838/sex-specific-molecular-responses-of-quick-to-court-protein-in-indian-malarial-vector-anopheles-culicifacies-conflict-of-mating-versus-blood-feeding-behaviour
#5
Tanwee Das De, Punita Sharma, Charu Rawal, Seena Kumari, Sanjay Tavetiya, Jyoti Yadav, Yasha Hasija, Rajnikant Dixit
Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28750681/drug-induced-amino-acid-deprivation-as-strategy-for-cancer-therapy
#6
REVIEW
Marcus Kwong Lam Fung, Godfrey Chi-Fung Chan
Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers...
July 27, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28746877/phospho-rasputin-stabilization-by-sec16-is-required-for-stress-granule-formation-upon-amino-acid-starvation
#7
Angelica Aguilera-Gomez, Margarita Zacharogianni, Marinke M van Oorschot, Heide Genau, Rianne Grond, Tineke Veenendaal, Kristina S Sinsimer, Elizabeth R Gavis, Christian Behrends, Catherine Rabouille
Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28745430/supplementation-of-nucleosides-during-selection-can-reduce-sequence-variant-levels-in-cho-cells-using-gs-msx-selection-system
#8
Danming Tang, Cynthia Lam, Salina Louie, Kam Hon Hoi, David Shaw, Mandy Yim, Brad Snedecor, Shahram Misaghi
In the process of generating stable monoclonal antibody (mAb) producing cell lines, reagents such as Methotrexate (MTX) or Methionine Sulfoximine (MSX) are often used. However, using such selection reagent(s) increases the possibility of having higher occurrence of sequence variants in the expressed antibody molecules due to the effects of MTX or MSX on de novo nucleotide synthesis. Since MSX inhibits glutamine synthase (GS) and results in both amino acid and nucleoside starvation, we questioned whether supplementing nucleosides into the media could lower sequence variant levels without affecting titer...
July 26, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28710039/cloning-expression-pattern-and-potential-role-of-apoptosis-inhibitor-5-in-the-termination-of-embryonic-diapause-and-early-embryo-development-of-artemia-sinica
#9
Shuang Zhang, Feng Yao, Ting Jing, Mengchen Zhang, Wei Zhao, Xiangyang Zou, Linlin Sui, Lin Hou
During the embryonic development of Artemia sinica, the diapause phenomenon can be induced by high salinity or low temperature conditions. The diapause embryo at the gastrula stage is maintained under the threat of apoptosis to guarantee the embryo's normal development. In this process, apoptosis inhibitor proteins play vital roles in protecting embryos against apoptosis. Apoptosis inhibitor5 (API5) plays a pivotal role in regulating the cell cycle and preventing programmed cell death after growth factor starvation...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28700931/feedback-inhibition-of-the-rag-gtpase-gap-complex-lst4-lst7-safeguards-torc1-from-hyperactivation-by-amino-acid-signals
#10
Marie-Pierre Péli-Gulli, Serena Raucci, Zehan Hu, Jörn Dengjel, Claudio De Virgilio
Amino acids stimulate the eukaryotic target of rapamycin complex 1 (TORC1), and hence growth, through the Rag GTPases and their regulators. Among these, the yeast Lst4-Lst7 Rag GTPase GAP complex clusters, as we previously reported, at the vacuolar membrane upon amino acid starvation. In response to amino acid refeeding, it activates the Rag GTPase-TORC1 branch and is then dispersed from the vacuolar surface. Here, we show that the latter effect is driven by TORC1 itself, which directly phosphorylates several residues within the intra-DENN loop of Lst4 that, only in its non-phosphorylated state, tethers the Lst4-Lst7 complex to the vacuolar membrane...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28690600/differential-growth-of-francisella-tularensis-which-alters-expression-of-virulence-factors-dominant-antigens-and-surface-carbohydrate-synthases-governs-the-apparent-virulence-of-ft-schus4-to-immunized-animals
#11
Kristen M Holland, Sarah J Rosa, Kolbrun Kristjansdottir, Donald Wolfgeher, Brian J Franz, Tiffany M Zarrella, Sudeep Kumar, Raju Sunagar, Anju Singh, Chandra S Bakshi, Prachi Namjoshi, Eileen M Barry, Timothy J Sellati, Stephen J Kron, Edmund J Gosselin, Douglas S Reed, Karsten R O Hazlett
The gram-negative bacterium Francisella tularensis (Ft) is both a potential biological weapon and a naturally occurring microbe that survives in arthropods, fresh water amoeba, and mammals with distinct phenotypes in various environments. Previously, we used a number of measurements to characterize Ft grown in Brain-Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and (2) slightly more virulent in naïve animals, compared to Ft grown in Mueller Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB repress expression of select Ft virulence factors by an unknown mechanism...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28668976/abscisic-acid-regulated-protein-degradation-causes-osmotic-stress-induced-accumulation-of-branched-chain-amino-acids-in-arabidopsis-thaliana
#12
Tengfang Huang, Georg Jander
Whereas proline accumulates through de novo biosynthesis in plants subjected to osmotic stress, leucine, isoleucine, and valine accumulation in drought-stressed Arabidopsis thaliana is caused by abscisic acid-regulated protein degradation. In response to several kinds of abiotic stress, plants greatly increase their accumulation of free amino acids. Although stress-induced proline increases have been studied the most extensively, the fold-increase of other amino acids, in particular branched-chain amino acids (BCAAs; leucine, isoleucine, and valine), is often higher than that of proline...
July 1, 2017: Planta
https://www.readbyqxmd.com/read/28655822/translation-initiation-from-conserved-non-aug-codons-provides-additional-layers-of-regulation-and-coding-capacity
#13
Ivaylo P Ivanov, Jiajie Wei, Stephen Z Caster, Kristina M Smith, Audrey M Michel, Ying Zhang, Andrew E Firth, Michael Freitag, Jay C Dunlap, Deborah Bell-Pedersen, John F Atkins, Matthew S Sachs
Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation...
June 27, 2017: MBio
https://www.readbyqxmd.com/read/28652262/identification-and-metabolite-profiling-of-chemical-activators-of-lipid-accumulation-in-green-algae
#14
Nishikant Wase, Boqiang Tu, James W Allen, Paul N Black, Concetta C DiRusso
Microalgae are proposed as feedstock organisms useful for producing biofuels and coproducts. However, several limitations must be overcome before algae-based production is economically feasible. Among these is the ability to induce lipid accumulation and storage without affecting biomass yield. To overcome this barrier, a chemical genetics approach was employed in which 43,783 compounds were screened against Chlamydomonas reinhardtii, and 243 compounds were identified that increase triacylglyceride (TAG) accumulation without terminating growth...
August 2017: Plant Physiology
https://www.readbyqxmd.com/read/28596215/reproductive-and-metabolic-state-differences-in-olfactory-responses-to-amino-acids-in-a-mouth-brooding-african-cichlid-fish
#15
Alexandre A Nikonov, Julie M Butler, Karen E Field, John Caprio, Karen P Maruska
Olfaction mediates many crucial life-history behaviors such as prey detection, predator avoidance, migration and reproduction. Olfactory function can also be modulated by an animal's internal physiological and metabolic states. While this is relatively well studied in mammals, little is known about how internal state impacts olfaction in fishes, the largest and most diverse group of vertebrates. Here we apply electro-olfactograms (EOGs) in the African cichlid fish Astatotilapia burtoni to test the hypothesis that olfactory responses to food-related cues (i...
August 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28593971/nutrient-acquisition-strategies-of-mammalian-cells
#16
Wilhelm Palm, Craig B Thompson
Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors...
June 7, 2017: Nature
https://www.readbyqxmd.com/read/28592812/activity-independent-targeting-of-mtor-to-lysosomes-in-primary-osteoclasts
#17
Andrew Wang, Luciene R Carraro-Lacroix, Celeste Owen, Bowen Gao, Paul N Corey, Pascal Tyrrell, John H Brumell, Irina Voronov
Mammalian target of rapamycin (mTOR) is activated by numerous stimuli, including amino acids and growth factors. This kinase is part of the mTOR complex 1 (mTORC1) which regulates cell proliferation, differentiation, and autophagy. Active mTORC1 is located on lysosomes and has been reported to disassociate from the lysosomal surface in the absence of amino acids. Furthermore, mTORC1 activity has been linked to the vacuolar H(+)-ATPases (V-ATPases), the proton pumps responsible for lysosomal acidification; however, the exact role of the V-ATPases in mTORC1 signaling is not known...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588606/mutations-in-the-not-genes-or-in-the-translation-machinery-similarly-display-increased-resistance-to-histidine-starvation
#18
Martine A Collart, Sari Kassem, Zoltan Villanyi
The NOT genes encode subunits of the conserved Ccr4-Not complex, a global regulator of gene expression, and in particular of mRNA metabolism. They were originally identified in a selection for increased resistance to histidine starvation in the yeast S. cerevisiae. Recent work indicated that the Not5 subunit, ortholog of mammalian CNOT3, determines global translation levels by defining binding of the Ccr4-Not scaffold protein Not1 to ribosomal mRNAs during transcription. This is needed for optimal translation of ribosomal proteins...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28566325/persistent-mtorc1-signaling-in-cell-senescence-results-from-defects-in-amino-acid-and-growth-factor-sensing
#19
Bernadette Carroll, Glyn Nelson, Yoana Rabanal-Ruiz, Olena Kucheryavenko, Natasha A Dunhill-Turner, Charlotte C Chesterman, Qabil Zahari, Tong Zhang, Sarah E Conduit, Christina A Mitchell, Oliver D K Maddocks, Penny Lovat, Thomas von Zglinicki, Viktor I Korolchuk
Mammalian target of rapamycin complex 1 (mTORC1) and cell senescence are intimately linked to each other and to organismal aging. Inhibition of mTORC1 is the best-known intervention to extend lifespan, and recent evidence suggests that clearance of senescent cells can also improve health and lifespan. Enhanced mTORC1 activity drives characteristic phenotypes of senescence, although the underlying mechanisms responsible for increased activity are not well understood. We have identified that in human fibroblasts rendered senescent by stress, replicative exhaustion, or oncogene activation, mTORC1 is constitutively active and resistant to serum and amino acid starvation...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28562106/enteral-nutrition-in-pediatric-intestinal-failure-does-initial-feeding-impact-on-intestinal-adaptation
#20
Teresa Capriati, Valerio Nobili, Laura Stronati, Salvatore Cucchiara, Francesca Laureti, Alessandra Liguori, Elaine Tyndall, Antonella Diamanti
Primary IF can be due to impaired gut length or impaired gut function; short bowel syndrome (SBS) is the leading cause of IF. In IF patients complete enteral starvation should be avoided whenever possible and enteral/oral nutrition (EN/ON) should be employed at the maximum tolerated amount in each phase of the clinical evolution of IF. Intraluminal nutrients have stimulatory effects on epithelial cells and on trophism that enhance intestinal adaptation. Areas covered: Evidence for nutritional interventions in pediatric IF is limited and of poor quality...
June 8, 2017: Expert Review of Gastroenterology & Hepatology
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