Disrupting the Myc-Tfeb circuit confers vulnerabilities targeting amino acid homeostasis and provokes metabolic anergy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA643255 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metabolic reprogramming sustains cancer cell anabolism, and MYC oncoproteins control many aspects of this response. Normal cells adapt to nutrient-limiting conditions by activating autophagy, which is required for amino acid (AA) homeostasis. Surprisingly, here we report the autophagy-lysosomal pathway is suppressed by Myc in normal B cells, in premalignant and neoplastic B cells of Eµ-Myc transgenic mice, and in MYC-driven human Burkitt lymphoma. Myc suppresses autophagy by antagonizing expression and function of TFEB, a master regulator of autophagy/lysosome genes. Notably, compensatory mechanisms that sustain AA pools in MYC-expressing B cells include marked increases in AA transport and coordinate induction of the proteasome. Finally, reactivation of the autophagy-lysosomal pathway by constitutively active TFEB disables the malignant state, by perturbing mitochondrial functions and disrupting proteasome activity, amino acid transport, and disrupts amino acid and nucleotide metabolism, leading to growth arrest and apoptosis. This scenario provides therapeutic opportunities that disable MYC-driven tumorigenesis, including AA restriction and treatment with proteasome inhibitors.
2022-02-27 | GSE153570 | GEO
Project description:T cell receptor(TCR) engagement in the absence of costimulation leads to a state of T cell tolerance known as anergy. Anergy induction requires new protein synthesis since it is inhibited by cycloheximide. In this experiment, we tried to figure out kinetic properties of the gene expression in anergy induction phase and the subsequent anergy maintenance phase.
2015-11-01 | GSE72731 | GEO
Project description:pooled mRNA (2, 4, 6 hrs) from A.E7 T cells under conditions which promote or inhibit anergy induction Keywords: ordered
2005-02-23 | GSE2323 | GEO
Project description:T cell receptor(TCR) engagement in the absence of costimulation leads to a state of T cell tolerance known as anergy. Anergy induction requires new protein synthesis since it is inhibited by cycloheximide. In this experiment, we tried to figure out kinetic properties of the gene expression in anergy induction phase and the subsequent anergy maintenance phase. A.E7 cell, a murine CD4(+) T cell clone, was stimulated with anti-TCR antibody for 0, 2, 4, and 6hrs followed by RNA extraction. For the maintenance phase, A.E7 was stimulated for 16hrs and rested for 5days before RNA extraction.
2015-11-01 | E-GEOD-72731 | biostudies-arrayexpress
Project description:In order to identify the effects of transcription factor EB (TFEB) overexpression on the liver transcriptome, we performed Affymetrix GeneChip hybridization experiments on injected mice overexpressing TFEB specifically in the liver. For the analysis of the injected mice overexpressing TFEB, total RNA was extracted from the liver of three mice. RNA extracted from the liver of 3 not-injected mice was used as a control.
2013-04-20 | E-GEOD-35015 | biostudies-arrayexpress
Project description:All animals have evolved the ability to survive nutrient deprivation, and nutrient signaling pathways are conserved modulators of health and disease. In C. elegans, late-larval starvation provokes adult reproductive diapause (ARD), a long-lived quiescent state that enables animals to survive months without food, yet underlying molecular mechanisms remain unknown. Here, we show that ARD is distinct from other forms of diapause, and shows surprisingly little requirement for canonical longevity pathways, autophagy and fat metabolism. Instead ARD depends dramatically on HLH-30/TFEB transcription factor to promote morphologic and metabolic remodeling involved in ARD entry, survival, and recovery, suggesting it is a master regulator of reproductive quiescence. TFEB transcriptome and genetic analyses reveal that Max-like HLH factors, mTOR, AMP-kinase, protein synthesis, and mitochondrial fusion are target processes that promote ARD longevity. Evidently reproductive quiescence rewires metabolism in unique ways to ensure long-term survival, and could illuminate similar mechanisms acting in latent tumorigenesis, and long-term fasting.
2020-03-30 | GSE126632 | GEO
Project description:Total RNA samples from three biological replicates in which TFEB was transiently overexpressed in HeLa cells by transfection using a pcDNA3 vector. As negative control, we used total RNA samples from HeLa cells transfected with an empty pcDNA3 vector. TFEB transfection
2010-04-09 | E-GEOD-16267 | biostudies-arrayexpress
Project description:T cell anergy is one of the mechanisms contributing to peripheral tolerance, particularly in the context of progressively growing tumors and in tolerogenic treatments promoting allograft acceptance. We recently reported that early growth response gene 2 (Egr2) is a critical transcription factor for the induction of anergy in vitro and in vivo, which was identified based on its ability to regulate the expression of inhibitory signaling molecules diacylglycerol kinase (DGK)-a and -z. We reasoned that other transcriptional targets of Egr2 might encode additional factors important for T cell anergy and immune regulation. Thus, we conducted two sets of genome-wide screens: gene expression profiling of wild type versus Egr2-deleted T cells treated under anergizing conditions, and a ChIP-Seq analysis to identify genes that bind Egr2 in anergic cells. Merging of these data sets revealed 49 targets that are directly regulated by Egr2. Among these are inhibitory signaling molecules previously reported to contribute to T cell anergy, but unexpectedly, also cell surface molecules and secreted factors, including lymphocyte-activation gene 3 (Lag3), Class-I-MHC-restricted T cell associated molecule (Crtam), Semaphorin 7A (Sema7A), and chemokine CCL1. These observations suggest that anergic T cells might not simply be functionally inert, and may have additional functional properties oriented towards other cellular components of the immune system.
2013-04-21 | GSE46242 | GEO
Project description:Expression data from Ppara (peroxisome proliferator activated receptor alpha) KO mice injected with TFEB specifically in liver. In order to identify the effects of TFEB overexpression together with Ppara absence on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice For the analysis on the injected Ppara-KO mice overexpressing TFEB, total RNA was extracted from the liver of three mice; RNA extracted from the liver of not-injected mice was used as control.
2013-04-20 | E-GEOD-41140 | biostudies-arrayexpress
Project description:In order to identify the effects of TFEB overexpression on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice For the analysis on the injected mice overexpressing TFEB, total RNA was extracted from the liver of three mice; RNA extracted from the liver of not-injected mice was used as control.
2013-04-20 | E-GEOD-41139 | biostudies-arrayexpress