Abstract:
:Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type-specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogenous glutamine for survival to justify the therapeutic targeting of glutamine metabolism, the mechanisms of glutamine dependence and likely response and resistance of such glutamine-targeting strategies among cancers are largely unknown. In this study, we have found a systematic variation in the glutamine dependence among breast tumor subtypes associated with mammary differentiation: basal- but not luminal-type breast cells are more glutamine-dependent and may be susceptible to glutamine-targeting therapeutics. Glutamine independence of luminal-type cells is associated mechanistically with lineage-specific expression of glutamine synthetase (GS). Luminal cells can also rescue basal cells in co-culture without glutamine, indicating a potential for glutamine symbiosis within breast ducts. The luminal-specific expression of GS is directly induced by GATA3 and represses glutaminase expression. Such distinct glutamine dependency and metabolic symbiosis is coupled with the acquisition of the GS and glutamine independence during the mammary differentiation program. Understanding the genetic circuitry governing distinct metabolic patterns is relevant to many symbiotic relationships among different cells and organisms. In addition, the ability of GS to predict patterns of glutamine metabolism and dependency among tumors is also crucial in the rational design and application of glutamine and other metabolic pathway targeted therapies.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Kung HN,Marks JR,Chi JTdoi
10.1371/journal.pgen.1002229subject
Has Abstractpub_date
2011-08-01 00:00:00pages
e1002229issue
8eissn
1553-7390issn
1553-7404pii
PGENETICS-D-11-00759journal_volume
7pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Genome-wide transcription start site (TSS) profiles of the enterobacteria Escherichia coli and Klebsiella pneumoniae were experimentally determined through modified 5' RACE followed by deep sequencing of intact primary mRNA. This identified 3,746 and 3,143 TSSs for E. coli and K. pneumoniae, respectively. Experimental...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002867
更新日期:2012-01-01 00:00:00
abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006080
更新日期:2016-05-23 00:00:00
abstract::Seedling establishment is inhibited on media containing high levels (∼ 6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a qua...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004213
更新日期:2014-03-13 00:00:00
abstract::Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella spec...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007389
更新日期:2018-05-14 00:00:00
abstract::Smc5/6, a member of the conserved SMC family of complexes, is essential for growth in most organisms. Its exact functions in a mitotic cell cycle are controversial, as chronic Smc5/6 loss-of-function alleles produce varying phenotypes. To circumvent this issue, we acutely depleted Smc5/6 in budding yeast and determine...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007129
更新日期:2018-01-23 00:00:00
abstract::While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002003
更新日期:2011-02-03 00:00:00
abstract::Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especia...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002865
更新日期:2012-01-01 00:00:00
abstract::The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001183
更新日期:2010-10-28 00:00:00
abstract::Studies in model organisms suggest that epistasis may play an important role in the etiology of complex diseases and traits in humans. With the era of large-scale genome-wide association studies fast approaching, it is important to quantify whether it will be possible to detect interacting loci using realistic sample ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020157
更新日期:2006-09-22 00:00:00
abstract::Target of Rapamycin (TOR) signalling allows eukaryotic cells to adjust cell growth in response to changes in their nutritional and environmental context. The two distinct TOR complexes (TORC1/2) localise to the cell's internal membrane compartments; the endoplasmic reticulum (ER), Golgi apparatus and lysosomes/vacuole...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006041
更新日期:2016-05-18 00:00:00
abstract::The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030120
更新日期:2007-07-01 00:00:00
abstract::The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000133
更新日期:2008-07-25 00:00:00
abstract::Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease ph...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000399
更新日期:2009-03-01 00:00:00
abstract::Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004264
更新日期:2014-04-03 00:00:00
abstract::The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs). Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arra...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005653
更新日期:2015-12-31 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005131.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1006300
更新日期:2016-08-31 00:00:00
abstract::The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000648
更新日期:2009-09-01 00:00:00
abstract::During development of the cerebral cortex, neural stem cells (NSCs) divide symmetrically to proliferate and asymmetrically to generate neurons. Although faithful segregation of mitotic chromosomes is critical for NSC divisions, its fundamental mechanism remains unclear. A class of evolutionarily conserved protein comp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004847
更新日期:2014-12-04 00:00:00
abstract::Cis-regulation plays an essential role in the control of gene expression, and is particularly complex and poorly understood for developmental genes, which are subject to multiple levels of modulation. In this study, we performed a global analysis of the cis-acting elements involved in the control of the zebrafish deve...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007581
更新日期:2018-08-06 00:00:00
abstract::The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic en...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007369
更新日期:2018-05-11 00:00:00
abstract::Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Dro...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003970
更新日期:2013-01-01 00:00:00
abstract::The semidominant Danforth's short tail (Sd) mutation arose spontaneously in the 1920s. The homozygous Sd phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The Sd mutant phenotype mirrors features seen in human caudal malformation sy...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003205
更新日期:2013-01-01 00:00:00
abstract::Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm⁵U₃₄), 5-methoxycarbonylmethyluridine (mcm⁵U₃₄), and 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U₃₄) at wobble position in tRNA. These modified nucleosides are important for efficient dec...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002258
更新日期:2011-09-01 00:00:00
abstract::The C. elegans germline is pluripotent and mitotic, similar to self-renewing mammalian tissues. Apoptosis is triggered as part of the normal oogenesis program, and is increased in response to various stresses. Here, we examined the effect of endoplasmic reticulum (ER) stress on apoptosis in the C. elegans germline. We...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004747
更新日期:2014-10-23 00:00:00
abstract::The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like gr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006475
更新日期:2016-12-16 00:00:00
abstract::In plants, multiple detached tissues are capable of forming a pluripotent cell mass, termed callus, when cultured on media containing appropriate plant hormones. Recent studies demonstrated that callus resembles the root-tip meristem, even if it is derived from aerial organs. This finding improves our understanding of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002911
更新日期:2012-08-01 00:00:00
abstract::Plant microRNAs (miRNAs) are critical regulators of gene expression, however little attention has been given to the principles governing miRNA silencing efficacy. Here, we utilize the highly conserved Arabidopsis miR159-MYB33/MYB65 regulatory module to explore these principles. Firstly, we show that perfect central co...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004232
更新日期:2014-03-13 00:00:00
abstract::The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentall...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030204
更新日期:2007-11-01 00:00:00
abstract::Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton moti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004800
更新日期:2014-11-13 00:00:00
abstract::During neural circuit formation, most axons are guided to complex environments, coming into contact with multiple potential synaptic partners. However, it is critical that they recognize specific neurons with which to form synapses. Here, we utilize the split GFP-based marker Neuroligin-1 GFP Reconstitution Across Syn...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007312
更新日期:2018-05-09 00:00:00