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https://www.readbyqxmd.com/read/28212626/a-global-characterization-of-the-translational-and-transcriptional-programs-induced-by-methionine-restriction-through-ribosome-profiling-and-rna-seq
#1
Ke Zou, Qi Ouyang, Hao Li, Jiashun Zheng
BACKGROUND: Among twenty amino acids, methionine has a special role as it is coded by the translation initiation codon and methionyl-tRNAi (Met-tRNAi) is required for the assembly of the translation initiation complex. Thus methionine may play a special role in global gene regulation. Methionine has also been known to play important roles in cell growth, development, cancer, and aging. In this work, we characterize the translational and transcriptional programs induced by methionine restriction (MetR) and investigate the potential mechanisms through which methionine regulates gene expression, using the budding yeast S...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28209762/identification-of-genes-in-saccharomyces-cerevisiae-that-are-haploinsufficient-for-overcoming-amino-acid-starvation
#2
Nancy S Bae, Andrew P Seberg, Leslie P Carroll, Mark J Swanson
The yeast Saccharomyces cerevisiae responds to amino acid deprivation by activating a pathway conserved in eukaryotes to overcome the starvation stress. We have screened the entire yeast heterozygous deletion collection to identify strains haploinsufficient for growth in the presence of sulfometuron methyl, which causes starvation for isoleucine and valine. We have discovered that cells devoid of MET15 are sensitive to sulfometuron methyl, and loss of heterozygosity at the MET15 locus can complicate screening the heterozygous deletion collection...
February 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28209124/rna-seq-and-metabolomic-analyses-of-akt1-mediated-muscle-growth-reveals-regulation-of-regenerative-pathways-and-changes-in-the-muscle-secretome
#3
Chia-Ling Wu, Yoshinori Satomi, Kenneth Walsh
BACKGROUND: Skeletal muscle is a major regulator of systemic metabolism as it serves as the major site for glucose disposal and the main reservoir for amino acids. With aging, cachexia, starvation, and myositis, there is a preferential loss of fast glycolytic muscle fibers. We previously reported a mouse model in which a constitutively-active Akt transgene is induced to express in a subset of muscle groups leading to the hypertrophy of type IIb myofibers with an accompanying increase in strength...
February 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28193602/preference-for-and-learning-of-amino-acids-in-larval-drosophila
#4
Nana Kudow, Daisuke Miura, Michael Schleyer, Naoko Toshima, Bertram Gerber, Teiichi Tanimura
Relative to other nutrients, less is known about how animals sense amino acids and how behaviour is organized accordingly. This is a significant gap in our knowledge, because amino acids are required for protein synthesis-and hence for life as we know it. Choosing larvae as a study case, we provide the first systematic analysis of both the preference behaviour for and the learning of all 20 canonical amino acids in Drosophila We report that preference for individual amino acids differs according to the kind of amino acid, both in first-instar and in third-instar larvae...
February 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28179877/putative-membrane-bound-transporters-mfsd14a-and-mfsd14b-are-neuronal-and-affected-by-nutrient-availability
#5
Emilia Lekholm, Emelie Perland, Mikaela M Eriksson, Sofie V Hellsten, Frida A Lindberg, Jinar Rostami, Robert Fredriksson
Characterization of orphan transporters is of importance due to their involvement in cellular homeostasis but also in pharmacokinetics and pharmacodynamics. The tissue and cellular localization, as well as function, is still unknown for many of the solute carriers belonging to the major facilitator superfamily (MFS) Pfam clan. Here, we have characterized two putative novel transporters MFSD14A (HIAT1) and MFSD14B (HIATL1) in the mouse central nervous system and found protein staining throughout the adult mouse brain...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28174690/the-gene-expression-of-numerous-slc-transporters-is-altered-in-the-immortalized-hypothalamic-cell-line-n25-2-following-amino-acid-starvation
#6
Sofie V Hellsten, Emilia Lekholm, Tauseef Ahmad, Robert Fredriksson
Amino acids are known to play a key role in gene expression regulation, and in mammalian cells, amino acid signaling is mainly mediated via two pathways, the mammalian target of rapamycin complex 1 (mTORC1) pathway and the amino acid responsive (AAR) pathway. It is vital for cells to have a system to sense amino acid levels, in order to control protein and amino acid synthesis and catabolism. Amino acid transporters are crucial in these pathways, due to both their sensing and transport functions. In this large-scale study, an immortalized mouse hypothalamic cell line (N25/2) was used to study the gene expression changes following 1, 2, 3, 5 or 16 h of amino acid starvation...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28160489/sec16-in-conventional-and-unconventional-exocytosis-working-at-the-interface-of-membrane-traffic-and-secretory-autophagy
#7
REVIEW
Bor Luen Tang
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have however pointed towards a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28121493/atp-driven-and-ampk-independent-autophagy-in-an-early-branching-eukaryotic-parasite
#8
Feng-Jun Li, Zhi-Shen Xu, Andy D S Soo, Zhao-Rong Lun, Cynthia Y He
Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28121483/stress-induced-polyubiquitination-of-proteasomal-ubiquitin-receptors-targets-the-proteolytic-complex-for-autophagic-degradation
#9
Victoria Cohen-Kaplan, Aaron Ciechanover, Ido Livneh
Ubiquitin (Ub) is a small protein (8 kDa) found in all eukaryotic cells, which is conjugated covalently to numerous proteins, tagging them for recognition by a downstream effector. One of the best characterized functions of Ub is targeting proteins for either selective degradation by the proteasome, or for bulk degradation by the autophagy-lysosome system. The executing arm of the UPS is the 26S proteasome, a large multi-catalytic complex. While much is known about the synthesis and assembly of the proteasome's subunits, the mechanism(s) underlying its removal has remained obscure, similar to that of many other components of the ubiquitin-proteasome system...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28115345/sub-inhibitory-concentrations-of-bacteriostatic-antibiotics-induce-rela-dependent-and-rela-independent-tolerance-to-%C3%AE-lactams
#10
Pavel Kudrin, Vallo Varik, Sofia Raquel Alves Oliveira, Jelena Beljantseva, Teresa Del Peso Santos, Ievgen Dzhygyr, Dominik Rejman, Felipe Cava, Tanel Tenson, Vasili Hauryliuk
The nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence. During amino acid starvation, the Escherichia coli (p)ppGpp synthetase RelA is activated by deacylated tRNA in the ribosomal A-site. An increase in (p)ppGpp is believed to drive the formation of antibiotic-tolerant persister cells, prompting the development of strategies to inhibit (p)ppGpp synthesis. We show that in a biochemical system from purified E. coli components, the antibiotic thiostrepton efficiently inhibits RelA activation by the A-site tRNA...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#11
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28095488/metabolism-of-seriola-lalandi-during-starvation-as-revealed-by-fatty-acid-analysis-and-compound-specific-analysis-of-stable-isotopes-within-amino-acids
#12
Fernando Barreto-Curiel, Ulfert Focken, Louis R D'Abramo, María Teresa Viana
Fish starvation is defined as food deprivation for a long period of time, such that physiological processes become confined to basal metabolism. Starvation provides insights in physiological processes without interference from unknown factors in digestion and nutrient absorption occurring in fed state. Juveniles of amberjack Seriola lalandi were isotopically equilibrated to a formulated diet for 60 days. One treatment consisted of fish that continued to be fed and fish in the other treatment were not fed for 35 days...
2017: PloS One
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#13
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28077876/microenvironmental-autophagy-promotes-tumour-growth
#14
Nadja S Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W Schultz, Ashish Jain, Mohammed M Rahman, Kay O Schink, Theodossis A Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28071763/starved-epithelial-cells-uptake-extracellular-matrix-for-survival
#15
Taru Muranen, Marcin P Iwanicki, Natasha L Curry, Julie Hwang, Cory D DuBois, Jonathan L Coloff, Daniel S Hitchcock, Clary B Clish, Joan S Brugge, Nada Y Kalaany
Extracellular matrix adhesion is required for normal epithelial cell survival, nutrient uptake and metabolism. This requirement can be overcome by oncogene activation. Interestingly, inhibition of PI3K/mTOR leads to apoptosis of matrix-detached, but not matrix-attached cancer cells, suggesting that matrix-attached cells use alternate mechanisms to maintain nutrient supplies. Here we demonstrate that under conditions of dietary restriction or growth factor starvation, where PI3K/mTOR signalling is decreased, matrix-attached human mammary epithelial cells upregulate and internalize β4-integrin along with its matrix substrate, laminin...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28066817/transcriptional-profiling-of-the-oral-pathogen-streptococcus-mutans-in-response-to-competence-signaling-peptide-xip
#16
Iwona B Wenderska, Andrew Latos, Benjamin Pruitt, Sara Palmer, Grace Spatafora, Dilani B Senadheera, Dennis G Cvitkovitch
In the cariogenic Streptococcus mutans, competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S...
January 2017: MSystems
https://www.readbyqxmd.com/read/28062303/purification-and-characterization-of-bioactive-peptides-ryamide-and-cchamide-in-the-kuruma-shrimp-marsupenaeus-japonicus
#17
Tohru Mekata, Tomoya Kono, Jun Satoh, Morikatsu Yoshida, Kenji Mori, Takahiro Sato, Mikiya Miyazato, Takanori Ida
To understand the regulation systems of appetite, bioactive peptides from the kuruma shrimp Marsupenaeus japonicus (Mj) were isolated and purified by reverse pharmacological assays using CHO cells expressing the Drosophila melanogaster G-protein-coupled receptors (GPCRs) CG5811 (a RYamide receptor) or CG14593 (a CCHamide-2 receptor). Four peptides having binding activity to GPCRs were obtained and named Mj RYamide-1, Mj RYamide-2, Mj RYamide-3, and Mj CCHamide. Genes encoding the prepropeptides of these peptides were identified using kuruma shrimp transcriptome databases...
January 4, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28057755/general-control-nonderepressible-2-gcn2-kinase-inhibits-target-of-rapamycin-complex-1-in-response-to-amino-acid-starvation-in-saccharomyces-cerevisiae
#18
Wenjie Yuan, Shuguang Guo, Jiaoqi Gao, Mingming Zhong, Gonghong Yan, Wangmeng Wu, Yapeng Chao, Yu Jiang
In eukaryotic cells two conserved protein kinases Gcn2 and TOR complex 1 (TORC1) couple amino acid conditions to protein translation. Gcn2 functions as an amino acid sensor and is activated by uncharged tRNAs which accumulate when intracellular amino acids are limited. Activated Gcn2 phosphorylates and inhibits eukaryotic initiation factor-2α (eIF2α), resulting in repression of general protein synthesis. Like Gcn2, TORC1 is also involved in sensing amino acid conditions. However, the underlying mechanism remains unclear...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28039918/regulation-of-reserve-mobilisation-in-sunflower-during-late-seedling-establishment-in-continuous-darkness
#19
A P Avelino, D F A de Oliveira, H A da Silva, C E C de Macêdo, E L Voigt
Reserve mobilisation, metabolite partitioning and reserve-degrading enzyme activity were studied in sunflower seedlings cultivated in vitro under a 12-h photoperiod or in the dark to investigate the involvement of source-sink relation and carbon starvation in the regulation of reserve mobilisation under continuous darkness. Reserves, metabolites and enzyme activity were determined with standard spectrophotometric methods. At the first 24 h of treatment (acclimation phase), darkness did not affect growth, but restricted carbon and nitrogen use, as indicated by sugar and amino acid accumulation in the different seedling parts...
December 31, 2016: Plant Biology
https://www.readbyqxmd.com/read/28039084/halofuginone-enhances-the-chemo-sensitivity-of-cancer-cells-by-suppressing-nrf2-accumulation
#20
Kouhei Tsuchida, Tadayuki Tsujita, Makiko Hayashi, Asaka Ojima, Nadine Keleku-Lukwete, Fumiki Katsuoka, Akihito Otsuki, Haruhisa Kikuchi, Yoshiteru Oshima, Mikiko Suzuki, Masayuki Yamamoto
The KEAP1-NRF2 system regulates the cellular defence against oxidative and xenobiotic stresses. NRF2 is a transcription factor that activates the expression of cytoprotective genes encoding antioxidative, detoxifying and metabolic enzymes as well as transporters. Under normal conditions, KEAP1 represses NRF2 activity by degrading the NRF2 protein. When cells are exposed to stresses, KEAP1 stops promoting NRF2 degradation, and NRF2 rapidly accumulates and activates the transcription of target genes. Constitutive accumulation of NRF2 via a variety of mechanisms that disrupt KEAP1-mediated NRF2 degradation has been observed in various cancer types...
December 28, 2016: Free Radical Biology & Medicine
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