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amino acid starvation

Zhengqing Zhang, Huapeng Wang, Chunfeng Hao, Wei Zhang, Miaomiao Yang, Yong Chang, Menglou Li
Dastarcus helophoroides, which has a relatively longer lifespan compared to other insects, is one of the most effective natural enemies of many large-body long-horned beetles. Methuselah (Mth) is associated with the lifespan, stress resistance, and reproduction in Drosophila melanogaster, but Mth is not present in non-drosophiline insects. A number of methuselah-like genes (mth-likes, mthls) have been identified in non-drosophiline insects, but it is still unknown whether they are present in Dastarcus helophoroides...
October 21, 2016: Genes
Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4 which triggers its ubiquitination/proteolysis and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
V Coothankandaswamy, S Cao, Y Xu, P D Prasad, P K Singh, C P Reynolds, S Yang, J Ogura, V Ganapathy, Y D Bhutia
BACKGROUND AND PURPOSE: Pancreatic cancer is an often lethal solid tumor. There is an urgent need to identify new drug targets for this disease. Highly proliferating cancer cells have an increased demand for nutrients and hence need to upregulate selective amino acid transporters. Here we wanted to find out which amino acid transporters are upregulated in pancreatic cancer and whether any of these transporters has potential as a drug target for this deadly disease. EXPERIMENTAL APPROACH: Expression of amino acid transporters in pancreatic cancer was analyzed using publicly available microarray datasets, and the findings with the transporter SLC6A14 were validated by mRNA and protein analysis...
October 17, 2016: British Journal of Pharmacology
Jennifer Popko, Cornelia Herrfurth, Kirstin Feussner, Till Ischebeck, Tim Iven, Richard Haslam, Mary Hamilton, Olga Sayanova, Jonathan Napier, Inna Khozin-Goldberg, Ivo Feussner
Oleaginous microalgae are considered as a promising resource for the production of biofuels. Especially diatoms arouse interest as biofuel producers since they are most productive in carbon fixation and very flexible to environmental changes in the nature. Naturally, triacylglycerol (TAG) accumulation in algae only occurs under stress conditions like nitrogen-limitation. We focused on Phaeodactylum strain Pt4 (UTEX 646), because of its ability to grow in medium with low salinity and therefore being suited when saline water is less available or for wastewater cultivation strategies...
2016: PloS One
Weiwei Li, Ming Chen, Erhui Wang, Liqin Hu, Malcolm J Hawkesford, Li Zhong, Zhu Chen, Zhaoshi Xu, Liancheng Li, Yongbin Zhou, Changhong Guo, Youzhi Ma
BACKGROUND: Autophagy is a cellular degradation process that is highly evolutionarily-conserved in yeast, plants, and animals. In plants, autophagy plays important roles in regulating intracellular degradation and recycling of amino acids in response to nutrient starvation, senescence, and other environmental stresses. Foxtail millet (Setaria italica) has strong resistance to stresses and has been proposed as an ideal material for use in the study of the physiological mechanisms of abiotic stress tolerance in plants...
October 12, 2016: BMC Genomics
Tetsuya Kimura, Shigeyuki Nada, Noriko Takegahara, Tatsusada Okuno, Satoshi Nojima, Sujin Kang, Daisuke Ito, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuichi Mitsui, Natsuki Sakurai, Hana Sarashina-Kida, Masayuki Nishide, Yohei Maeda, Hyota Takamatsu, Daisuke Okuzaki, Masaki Yamada, Masato Okada, Atsushi Kumanogoh
Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H(+)-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization...
October 12, 2016: Nature Communications
Manpreet K Dhami, Thomas Hartwig, Tadashi Fukami
Priority effects, in which the order of species arrival dictates community assembly, can have a major influence on species diversity, but the genetic basis of priority effects remains unknown. Here, we suggest that nitrogen scavenging genes previously considered responsible for starvation avoidance may drive priority effects by causing rapid resource depletion. Using single-molecule sequencing, we de novo assembled the genome of the nectar-colonizing yeast, Metschnikowia reukaufii, across eight scaffolds and complete mitochondrion, with gap-free coverage over gene spaces...
October 12, 2016: Proceedings. Biological Sciences
Sensen Shen, Rui Weng, Linnan Li, Xinyuan Xu, Yu Bai, Huwei Liu
Autophagy-related protein 7 (Atg7) is essential in the formation of the autophagophore and is indispensable for autophagy induction. Autophagy will exist in lower level or even be blocked in cells without Atg7. Even though the possible signaling pathways of Atg7 have been proposed, the metabolomic responses under acute starvation in cells with and without Atg7 have not been elucidated. This study therefore was designed and aimed to reveal the metabolomics of Atg7-dependent autophagy through metabolomic analysis of Atg7(-/-) mouse embryonic fibroblast cells (MEFs) and wild-type MEFs along with the starvation time...
October 5, 2016: Scientific Reports
Shardulendra Sherchand, Joyce A Ibana, Alison J Quayle, Ashok Aiyar
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that cannot synthesize several amino acids, including tryptophan. Rather, C. trachomatis acquires these essential metabolites from its human host cell. Chlamydial dependence on host-provided tryptophan underlies a major host defense mechanism against the bacterium; namely, the induction of the host tryptophan-catabolizing enzyme, indoleamine 2,3- dioxygenase (IDO1) by interferon gamma (IFNγ), which leads to eradication of C. trachomatis by tryptophan starvation...
August 2016: Journal of Bacteriology & Parasitology
Dan-Dan Guo, Wen-Zhi Guan, Yi-Wen Sun, Jie Chen, Xia-Yun Jiang, Shu-Ming Zou
Fibroblast growth factor 1 (Fgf1) is known as a mitogenic factor involved in the regulation of cell growth, proliferation, and differentiation in vertebrates. Here, we report the isolation and characterization of two fgf1 genes in grass carp (Ctenopharyngodon idella). Grass carp fgf1a and fgf1b cDNAs are highly divergent, sharing a relatively low amino acid sequence identity of 50%, probably due to fish-specific gene duplication. fgf1a and fgf1b mRNAs were detected in the zygote and expressed throughout embryogenesis...
September 24, 2016: General and Comparative Endocrinology
Lauren R Walling, J Scott Butler
: Toxin-antitoxin (TA) systems are ubiquitous in bacteria and archaea, where they play a pivotal role in the establishment and maintenance of dormancy. Under normal growth conditions, the antitoxin neutralizes the toxin. However, under conditions of stress, such as nutrient starvation or antibiotic treatment, cellular proteases degrade the antitoxin, and the toxin functions to arrest bacterial growth. We characterized the specificity determinants of the interactions between VapB antitoxins and VapC toxins from nontypeable Haemophilus influenzae (NTHi) in an effort to gain a better understanding of how antitoxins control toxin activity and bacterial persistence...
September 26, 2016: Journal of Bacteriology
Youheng Wei, Brad Reveal, Weili Cai, Mary A Lilly
TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionary conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here we characterize null mutants of the GATOR1 components nprl2, nprl3 and iml1 in Drosophila melanogaster We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability...
September 26, 2016: G3: Genes—Genomes—Genetics
Savita Saini, Ayan Kumar Ghosh, Ruby Singh, Sushmita Das, Kumar Abhishek, Ajay Kumar, Sudha Verma, Abhishek Mandal, Abul Hasan Sardar, Bidyut Purkait, Ashish Kumar, Kislay Kumar Sinha, Pradeep Das
Various physiological stimuli trigger the conversion of non-infective L. donovani promastigotes to the infective form. Here we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. Glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. However, this was reversed by supplementation of gluconeogenic amino acids. Glucose starvation induced metacyclogenesis and enhanced virulence through protein kinase A regulatory subunit (LdPKAR1) mediated autophagy...
September 24, 2016: Molecular Microbiology
Elina Timosenko, Hemza Ghadbane, Jonathan D Silk, Dawn Shepherd, Uzi Gileadi, Lauren J Howson, Robert Laynes, Qi Zhao, Robert L Strausberg, Lars R Olsen, Stephen Taylor, Francesca M Buffa, Richard Boyd, Vincenzo Cerundolo
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms. which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be up-regulated in resting human T cells kept under low tryptophan conditions, but was enhanced upon cognate antigen T cell receptor engagement...
September 20, 2016: Cancer Research
Shusuke Taniuchi, Masato Miyake, Kazue Tsugawa, Miho Oyadomari, Seiichi Oyadomari
The integrated stress response (ISR) is a cytoprotective pathway initiated upon phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α) residue designated serine-51, which is critical for translational control in response to various stress conditions. Four eIF2α kinases, namely heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2), have been identified thus far, and they are known to be activated by heme depletion, viral infection, endoplasmic reticulum stress, and amino acid starvation, respectively...
2016: Scientific Reports
Nisebita Sahu, Darlene Dela Cruz, Min Gao, Wendy Sandoval, Peter M Haverty, Jinfeng Liu, Jean-Philippe Stephan, Benjamin Haley, Marie Classon, Georgia Hatzivassiliou, Jeff Settleman
The role of essential amino acids in metabolic reprogramming of cancer cells is now well established, whereas the role of non-essential amino acids (NEAAs) in malignancy remains less clear. Here, we have identified an important role for the NEAA proline in the tumorigenic potential of a subset of cancer cells. By profiling a large panel of cancer cell lines, we observed that proline consumption and expression of proline biosynthesis enzymes were well correlated with clonogenic and tumorigenic potential. Moreover, proline starvation or inhibition of proline biosynthesis enzymes impaired clonogenic/tumorigenic potential...
September 3, 2016: Cell Metabolism
Mridusmita Saikia, Xiaoyun Wang, Yuanhui Mao, Ji Wan, Tao Pan, Shu-Bing Qian
It is common wisdom that codon usage bias has evolved in the selection for efficient translation, in which highly expressed genes are encoded predominantly by optimal codons. However, a growing body of evidence suggests regulatory roles for non-optimal codons in translation dynamics. Here we report that in mammalian cells, non-optimal codons play a critical role in promoting selective mRNA translation during amino acid starvation. During starvation, in contrast to genes encoding ribosomal proteins whose translation is highly sensitive to amino acid deprivation, translation of genes involved in the cellular protein degradation pathways remains unaffected...
September 9, 2016: RNA
Gabriela Páchniková, Stjepan Uldrijan, Aleš Imramovský, Vladimír Kryštof, Iva Slaninová
N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (Compound 6k), was recently isolated during the preparation of amino acids esters with salicylanilides. We show here that 6k disrupts the dynamics of actin cytoskeleton in human melanoma cells, affecting processes essential for the maintenance and expansion of tumours such as cell adhesion, motility, proliferation, vesicular transport, and autophagic flux. We demonstrated that inhibition of autophagy by 6k increased the sensitivity of melanoma cells to metabolic stress induced by rotenone or nutrient starvation and potentiated the anti-proliferative activity of small molecule multikinase inhibitor sorafenib...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
José Miguel Flores Fernández, Carla Patricia Barragán Álvarez, Carla Vanessa Sánchez Hernández, Eduardo Padilla Camberos, Celia González Castillo, Daniel Ortuño Sahagún, Moisés Martínez Velázquez
The cattle tick Rhipicephalus (Boophilus) microplus is a hematophagous ectoparasite of major importance for the livestock industry. It shows a remarkable ability to survive over long periods without feeding. However, the mechanisms used to endure long-term starvation are poorly understood. It is believed that autophagy, a process of intracellular protein degradation, may play a significant role to confront adverse environmental conditions. To advance our understanding of autophagy in R. microplus, in the present study we report the molecular characterization of three autophagy-related (ATG) genes, namely, RmATG3, RmATG4 and RmATG6, as well as their expression profiles in different developmental stages and organs of the parasite...
November 2016: Parasitology
Graeme Sargent, Tim van Zutphen, Tatiana Shatseva, Ling Zhang, Valeria Di Giovanni, Robert Bandsma, Peter Kijun Kim
Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy...
September 12, 2016: Journal of Cell Biology
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