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  • 1
    Publication Date: 2011-11-22
    Description: Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of alpha-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived alpha-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710581/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Metallo, Christian M -- Gameiro, Paulo A -- Bell, Eric L -- Mattaini, Katherine R -- Yang, Juanjuan -- Hiller, Karsten -- Jewell, Christopher M -- Johnson, Zachary R -- Irvine, Darrell J -- Guarente, Leonard -- Kelleher, Joanne K -- Vander Heiden, Matthew G -- Iliopoulos, Othon -- Stephanopoulos, Gregory -- P30 CA014051/CA/NCI NIH HHS/ -- R01 CA122591/CA/NCI NIH HHS/ -- R01 DK075850-01/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Nov 20;481(7381):380-4. doi: 10.1038/nature10602.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22101433" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyl Coenzyme A/biosynthesis/metabolism ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; CD8-Positive T-Lymphocytes/cytology ; Carbon/metabolism ; Carcinoma, Renal Cell/metabolism/pathology ; *Cell Hypoxia ; Cell Line, Tumor ; Cells, Cultured ; Citric Acid Cycle ; Glutamine/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Isocitrate Dehydrogenase/deficiency/genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Kidney Neoplasms/metabolism/pathology ; *Lipogenesis ; Oxidation-Reduction ; Oxygen/metabolism ; Palmitic Acid/metabolism ; Von Hippel-Lindau Tumor Suppressor Protein/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2006-12-13
    Description: Global transcription machinery engineering (gTME) is an approach for reprogramming gene transcription to elicit cellular phenotypes important for technological applications. Here we show the application of gTME to Saccharomyces cerevisiae for improved glucose/ethanol tolerance, a key trait for many biofuels programs. Mutagenesis of the transcription factor Spt15p and selection led to dominant mutations that conferred increased tolerance and more efficient glucose conversion to ethanol. The desired phenotype results from the combined effect of three separate mutations in the SPT15 gene [serine substituted for phenylalanine (Phe(177)Ser) and, similarly, Tyr(195)His, and Lys(218)Arg]. Thus, gTME can provide a route to complex phenotypes that are not readily accessible by traditional methods.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alper, Hal -- Moxley, Joel -- Nevoigt, Elke -- Fink, Gerald R -- Stephanopoulos, Gregory -- GM035010/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Dec 8;314(5805):1565-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17158319" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Cell Cycle Proteins/*genetics/metabolism ; Ethanol/*metabolism/pharmacology ; Fermentation ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; *Genetic Engineering ; Glucose/metabolism/pharmacology ; Mutagenesis ; Phenotype ; Saccharomyces cerevisiae/*genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; TATA-Binding Protein Associated Factors/genetics/metabolism ; TATA-Box Binding Protein/*genetics/metabolism ; Transcription Factor TFIID/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; *Transcription, Genetic ; Transformation, Genetic ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1991-06-21
    Description: In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist flux alterations at branch points. This problem can be addressed through the use of some general concepts of metabolic rigidity, which include a means for identifying and removing rigid branch points within an experimental framework.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephanopoulos, G -- Vallino, J J -- New York, N.Y. -- Science. 1991 Jun 21;252(5013):1675-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1904627" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Dioxide/metabolism ; Corynebacterium/*metabolism ; Enzymes/metabolism ; Genetic Engineering/*methods ; Glucose/metabolism ; Lysine/*biosynthesis ; *Metabolism ; NADP/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephanopoulos, G -- Kelleher, J -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2024-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. gregstep@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408647" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; *Cell Physiological Phenomena ; Diatoms/*genetics/*metabolism ; Gene Expression Regulation ; *Genetic Engineering ; Genetic Therapy ; Glucose/metabolism ; Glucose Transporter Type 1 ; Humans ; Metabolic Diseases/therapy ; Models, Biological ; Models, Genetic ; Monosaccharide Transport Proteins/*genetics/metabolism ; Photosynthesis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-10
    Description: Economic and geopolitical factors (high oil prices, environmental concerns, and supply instability) have been prompting policy-makers to put added emphasis on renewable energy sources. For the scientific community, recent advances, embodied in new insights into basic biology and technology that can be applied to metabolic engineering, are generating considerable excitement. There is justified optimism that the full potential of biofuel production from cellulosic biomass will be obtainable in the next 10 to 15 years.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephanopoulos, Gregory -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):801-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. gregstep@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289987" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/genetics/*metabolism ; *Biomass ; Bioreactors ; *Biotechnology/economics/instrumentation/methods ; Carbohydrate Metabolism ; Cellulose/metabolism ; Costs and Cost Analysis ; *Energy-Generating Resources/economics ; Ethanol/metabolism ; Fermentation ; Fungi/genetics/*metabolism ; *Genetic Engineering ; Hydrolysis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2004-04-17
    Description: Pathway optimization is difficult to achieve owing to complex, nonlinear, and largely unknown interactions of enzymes, regulators, and metabolites. We report a pathway reconstruction using RNA display-derived messenger RNA-enzyme fusion molecules. These chimeras are immobilized by hybridization of their messenger RNA end with homologous capture DNA spotted on a substrate surface. Enzymes thus immobilized retain activity proportional to the amount of capture DNA, allowing modulation of the relative activity of pathway enzymes. Entire pathways can thus be reconstructed and optimized in vitro from genomic information. We provide concept validation with the sequential reactions catalyzed by luciferase and nucleoside diphosphate kinase and further illustrate this method with the optimization of the five-step pathway for trehalose synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jung, Gyoo Yeol -- Stephanopoulos, Gregory -- New York, N.Y. -- Science. 2004 Apr 16;304(5669):428-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15087547" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; DNA/genetics/metabolism ; Enzymes, Immobilized/genetics/*metabolism ; Gene Expression ; *Gene Expression Profiling ; *Genetic Engineering ; Glucose/metabolism ; Glucosyltransferases/genetics/metabolism ; Hexokinase/genetics/metabolism ; Kinetics ; Luciferases/genetics/metabolism ; *Metabolism ; Nucleic Acid Hybridization ; Nucleoside-Diphosphate Kinase/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphoglucomutase/genetics/metabolism ; Phosphoric Monoester Hydrolases/genetics/metabolism ; *Protein Array Analysis ; Protein Biosynthesis ; RNA, Messenger/*metabolism ; Trehalose/*biosynthesis ; UTP-Glucose-1-Phosphate Uridylyltransferase/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2010-10-12
    Description: Taxol (paclitaxel) is a potent anticancer drug first isolated from the Taxus brevifolia Pacific yew tree. Currently, cost-efficient production of Taxol and its analogs remains limited. Here, we report a multivariate-modular approach to metabolic-pathway engineering that succeeded in increasing titers of taxadiene--the first committed Taxol intermediate--approximately 1 gram per liter (~15,000-fold) in an engineered Escherichia coli strain. Our approach partitioned the taxadiene metabolic pathway into two modules: a native upstream methylerythritol-phosphate (MEP) pathway forming isopentenyl pyrophosphate and a heterologous downstream terpenoid-forming pathway. Systematic multivariate search identified conditions that optimally balance the two pathway modules so as to maximize the taxadiene production with minimal accumulation of indole, which is an inhibitory compound found here. We also engineered the next step in Taxol biosynthesis, a P450-mediated 5alpha-oxidation of taxadiene to taxadien-5alpha-ol. More broadly, the modular pathway engineering approach helped to unlock the potential of the MEP pathway for the engineered production of terpenoid natural products.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034138/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034138/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ajikumar, Parayil Kumaran -- Xiao, Wen-Hai -- Tyo, Keith E J -- Wang, Yong -- Simeon, Fritz -- Leonard, Effendi -- Mucha, Oliver -- Phon, Too Heng -- Pfeifer, Blaine -- Stephanopoulos, Gregory -- 1-R01-GM085323-01A1/GM/NIGMS NIH HHS/ -- R01 GM085323/GM/NIGMS NIH HHS/ -- R01 GM085323-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):70-4. doi: 10.1126/science.1191652.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929806" target="_blank"〉PubMed〈/a〉
    Keywords: Alkenes/*metabolism ; Bioreactors ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Diterpenes/*metabolism ; Erythritol/analogs & derivatives/metabolism ; Escherichia coli K12/enzymology/genetics/*metabolism ; Farnesyltranstransferase/genetics/metabolism ; Fermentation ; *Genetic Engineering ; Hemiterpenes/metabolism ; Indoles/metabolism ; Isomerases/genetics/metabolism ; Metabolic Networks and Pathways/genetics ; Metabolomics ; NADPH-Ferrihemoprotein Reductase/genetics/metabolism ; Organophosphorus Compounds/metabolism ; Oxidation-Reduction ; Paclitaxel/*biosynthesis ; Recombinant Fusion Proteins/metabolism ; Sugar Phosphates/metabolism ; Taxoids/metabolism ; Taxus/enzymology ; Terpenes/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-10-04
    Description: Ethanol toxicity in the yeast Saccharomyces cerevisiae limits titer and productivity in the industrial production of transportation bioethanol. We show that strengthening the opposing potassium and proton electrochemical membrane gradients is a mechanism that enhances general resistance to multiple alcohols. The elevation of extracellular potassium and pH physically bolsters these gradients, increasing tolerance to higher alcohols and ethanol fermentation in commercial and laboratory strains (including a xylose-fermenting strain) under industrial-like conditions. Production per cell remains largely unchanged, with improvements deriving from heightened population viability. Likewise, up-regulation of the potassium and proton pumps in the laboratory strain enhances performance to levels exceeding those of industrial strains. Although genetically complex, alcohol tolerance can thus be dominated by a single cellular process, one controlled by a major physicochemical component but amenable to biological augmentation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401034/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Felix H -- Ghaderi, Adel -- Fink, Gerald R -- Stephanopoulos, Gregory -- R01 GM035010/GM/NIGMS NIH HHS/ -- R01-GM035010/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):71-5. doi: 10.1126/science.1257859. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. Whitehead Institute for Biomedical Research, Cambridge, MA, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278607" target="_blank"〉PubMed〈/a〉
    Keywords: *Biofuels ; Cation Transport Proteins/genetics ; Cell Culture Techniques ; Cell Membrane/metabolism ; Chemical Engineering ; *Drug Resistance, Fungal/genetics ; Ethanol/*metabolism/pharmacology ; Fermentation ; Genetic Engineering ; Glucose/metabolism ; Hydrogen-Ion Concentration ; Phosphates/*metabolism ; Potassium Compounds/*metabolism ; Proton Pumps/genetics ; Proton-Translocating ATPases/genetics ; Saccharomyces cerevisiae/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Up-Regulation ; Xylose/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-08-28
    Description: Populations of microorganisms inhabiting a common environment complete for nutrients and other resources of the environment. In some cases, the populations even excrete into the environment chemicals that are toxic or inhibitory to their competitors. Competition between two populations tends to eliminate one of the populations from their common habitat, especially when competition is focused on a single resource and when the populations do not otherwise interact. However, a number of factors mitigate the severity of competition and thus competitors often coexist.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fredrickson, A G -- Stephanopoulos, G -- New York, N.Y. -- Science. 1981 Aug 28;213(4511):972-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7268409" target="_blank"〉PubMed〈/a〉
    Keywords: *Bacterial Physiological Phenomena ; Ecology ; Energy Metabolism ; Environment ; Eukaryota/*physiology ; Growth ; Population Dynamics ; Yeasts/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-15
    Description: Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers. The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. Here we show that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors. In human PDA cells, the MiT/TFE proteins--MITF, TFE3 and TFEB--are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosome activation is specifically required to maintain intracellular amino acid pools. These results identify the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrate that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perera, Rushika M -- Stoykova, Svetlana -- Nicolay, Brandon N -- Ross, Kenneth N -- Fitamant, Julien -- Boukhali, Myriam -- Lengrand, Justine -- Deshpande, Vikram -- Selig, Martin K -- Ferrone, Cristina R -- Settleman, Jeff -- Stephanopoulos, Gregory -- Dyson, Nicholas J -- Zoncu, Roberto -- Ramaswamy, Sridhar -- Haas, Wilhelm -- Bardeesy, Nabeel -- DP2 CA195761/CA/NCI NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- P01 CA117969-07/CA/NCI NIH HHS/ -- P50CA1270003/CA/NCI NIH HHS/ -- R01 CA133557-05/CA/NCI NIH HHS/ -- England -- Nature. 2015 Aug 20;524(7565):361-5. doi: 10.1038/nature14587. Epub 2015 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26168401" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acids/metabolism ; Animals ; Autophagy/*genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Carcinoma, Pancreatic Ductal/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Energy Metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Heterografts ; Homeostasis ; Humans ; Lysosomes/genetics/*metabolism ; Mice ; Microphthalmia-Associated Transcription Factor/metabolism ; Neoplasm Transplantation ; Pancreatic Neoplasms/genetics/*metabolism/*pathology ; Transcription Factors/*metabolism ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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