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Open AccessGlobal alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis
Metabolic obstacles of the tumor microenvironment remain a challenge to T-cell-mediated cancer immunotherapies. To better understand the interplay of immune checkpoint signaling and immune metabolism, this stu...
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Mitochondrial metabolism and glutamine are essential for mesoderm differentiation of human pluripotent stem cells
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Open AccessAmpk regulates IgD expression but not energy stress with B cell activation
Ampk is an energy gatekeeper that responds to decreases in ATP by inhibiting energy-consuming anabolic processes and promoting energy-generating catabolic processes. Recently, we showed that Lkb1, an understud...
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Article
Open AccessA precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers
Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have n...
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Article
Author Correction: Metabolic gatekeeper function of B-lymphoid transcription factors
In Fig. 3c of this Letter, the the effects of CRISPR–Cas9-mediated deletion of NR3C1, TXNIP and CNR2 in patient-derived B-lineage leukaemia cells were shown. For curves depicting NR3C1 (left graph), data s for TX...
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Open AccessMetabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities
There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exo...
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Article
Lactate dehydrogenase activity drives hair follicle stem cell activation
Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic m...
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Article
Open AccessATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibit...
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Article
Metabolic gatekeeper function of B-lymphoid transcription factors
The B-lymphoid transcription factors PAX5 and IKZF1 restrict the supply of glucose and energy to B cells to levels that are not enough to fuel a driver-oncogene, thereby acting as tumour suppressors and sensit...
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Article
Open AccessAsparagine promotes cancer cell proliferation through use as an amino acid exchange factor
Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine...
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Open AccessMYC-induced reprogramming of glutamine catabolism supports optimal virus replication
Viruses rewire host cell glucose and glutamine metabolism to meet the bioenergetic and biosynthetic demands of viral propagation. However, the mechanism by which viruses reprogram glutamine metabolism and the ...
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Article
The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR
Ageing in the worm Caenorhabditis elegans is shown to be delayed by supplementation with α-ketoglutarate, an effect that is probably mediated by ATP synthase—which is identified as a direct target of α-ketoglutar...
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Open AccessThe promoter regions of the Myb-regulated Adora2B and Mcm4 genes co-localize with origins of DNA replication
The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). v-Myb is thought to exert its biologic...
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Identification of a Myb-responsive enhancer of the chicken C/EBPβ gene
The retroviral oncogene v-myb encodes a transcription factor (v-Myb) that disrupts myelomonocytic differentiation and transforms myelomonocytic cells. It is thought that the biological effects of v-Myb are caused...