Microarray analysis of TFEB-regulated genes in vascular smooth muscle cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138000 | GEO | 2020/11/21
REPOSITORIES: GEO
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Project description:Transcription factro-EB (TFEB) is a master gene for autophagy and lysosome biogenesis We used microarrays to detail the gene expression in TFEB-overexpressing endothelial cells and identified distinct classes of TFEB-regulated genes.
2018-05-01 | GSE108384 | GEO
Project description:The transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy. We identify a distinct nuclear interactome of TFEB, with USP7 emerging as a key post-translational modulator of TFEB. Genetic depletion and inhibition of USP7 reveal its critical role in preserving TFEB stability within both nuclear and cytoplasmic compartments. Specifically, USP7 is identified as the deubiquitinase responsible for removing the K48-linked polyubiquitination signal from TFEB at lysine residues K116, K264, and K274, thereby preventing its proteasomal degradation. Functional assays demonstrate the involvement of USP7 in preserving TFEB-mediated transcriptional responses to nutrient deprivation, while also modulating autophagy flux and lysosome biogenesis. As USP7 is a deubiquitinase that protects TFEB from proteasomal degradation, these findings provide the foundation for therapeutic targeting of the USP7-TFEB axis in conditions characterized by TFEB dysregulation and metabolic abnormalities, particularly in certain cancers.
2024-09-17 | PXD055937 | Pride
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:Lysosomes are at the epicenter of cellular processes critical for inflammasome activation in macrophages, including autophagy and lipid metabolism. Inflammasome activation and IL1-beta secretion are implicated in atherogenesis, ischemic cardiac injury and resultant heart failure; however, little is known about the role of macrophage lysosome function in regulating these processes. We hypothesized that macrophages exhibit lysosome dysfunction in heart failure due to ischemic injury, and that augmentation of macrophage lysosomal biogenesis via macrophage-specific overexpression of transcription factor EB (mf-TFEB) would attenuate ischemic remodeling by modulating macrophage inflammatory responses. In both mice subject to ischemia-reperfusion injury, and human heart tissue from patients with ischemic cardiomyopathy, we find evidence of lysosome insufficiency and autophagic impairment, respectively. Mf-TFEB overexpression significantly attenuated post-IR adverse left ventricular remodeling at 4 weeks without affecting scar size. Mf-TFEB overexpression reduced the relative amounts of pro-inflammatory macrophage populations in the myocardium. RNA sequencing of flow-sorted cardiac macrophages post-IR confirmed that TFEB stimulated a lysosomal transcriptional program in macrophages, and upregulated key targets involved in lysosomal lipid metabolism, which we show are critical for inflammasome suppression. Both TFEB-dependent inflammasome suppression and effects on post-IR remodeling were independent of autophagy. Our findings suggest that TFEB reprograms macrophage lysosomal lipid metabolism to attenuate inflammasome activity and protect against post-ischemic cardiac remodeling and simultaneously shift our understanding of how autophagy and lipid metabolism impact acute inflammation.
2019-11-01 | GSE118463 | GEO
Project description:How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3 phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognised nuclear export signal (NES). Importantly, GSK3 is inactivated by AKT in response to mTORC2 signalling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.
2018-10-18 | PXD009677 | Pride
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.
2013-04-20 | GSE35015 | GEO
Project description:Lysosome-mediated macroautophagy, including lipophagy, is activated under nutrient deprivation but is repressed after feeding. We show that feeding unexpectedly activates intestinal lipophagy in a manner dependent on both the orphan nuclear receptor, small heterodimer partner (SHP/NR0B2), and the late fed-state gut hormone, fibroblast growth factor-15/19 (FGF15/19). Postprandial intestinal triglycerides (TGs) and apolipoprotein-B48 (ApoB48), the TG-rich chylomicron marker, were elevated in SHP-knockout and FGF15-knockout mice. Genomic analyses in mouse intestine revealed that SHP partners with the key lysosomal activator, transcription factor-EB (TFEB), upregulating autophagy/lipolysis network genes after feeding. In HT29 intestinal cells, FGF19 treatment activated lipophagy in a manner dependent on both SHP and TFEB, reducing TG and ApoB48 levels. Mechanistically, feeding-induced FGF15/19 signaling increases nuclear localization of TFEB and SHP via PKCβ/ζ-mediated phosphorylation, leading to transcriptional induction of Ulk1 and Atgl. Collectively, these results demonstrate that after feeding, FGF15/19-activated SHP and TFEB paradoxically activate gut lipophagy, limiting postprandial TG levels. As excess lipids cause dyslipidemia and obesity, the FGF15/19-SHP-TFEB axis that reduces intestinal TGs via lipophagic activation provides promising therapeutic targets for obesity-associated metabolic disease.
2022-04-22 | GSE197549 | GEO
Project description:Our studies in Salmonella Typhimurium (S. Typhimurium)-infected cells indicate that TFEB has a non-transcriptional, cytosolic function in addition to its well-characterized role as a transcription factor in regulating autophagy and lysosome biogenesis. An unbiased proteomics approach revealed that TFEB interacts with several mitochondrial proteins, which is lost when infected with S. Typhimurium. Microscopical and biochemical examinations further confirmed a novel localization of TFEB in mitochondria. We have also identified a TOMM20 binding motif within the protein sequence of TFEB which, facilitates the mitochondrial translocation in a mTOR-dependent manner. Our results further demonstrate that TFEB and the mitochondrial protease LonP1 co-regulate the assembly of complex I and its function. Moreover, during S. Typhimurium infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines.
2024-05-21 | PXD013758 | Pride
Project description:Transcription factor EB (TFEB) mediates gene expression through binding to the Coordinated Lysosome Expression And Regulation (CLEAR) sequence. We created a knock-in mouse line in which the CLEAR sequence of ATP6V1H was mutated. Crossing the CLEAR mutant with PS19 mice led to higher tau pathology but dampened glial cell activation. snRNA-seq revealed that the CLEAR mutant failed to be activated in tauopathy conditions.
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Project description:Sexual dimorphism affects diverse biological functions such as immune responses. However, mechanisms by which different sexes alter immunity remained largely unknown. By using Caenorhabditis elegans as a model, here we show that male animals exhibit enhanced immunity against various pathogenic bacteria via upregulating autophagy. We found that male C. elegans displayed upregulation of helix loop helix 30 (HLH-30)/transcription factor EB (TFEB), a transcription factor crucial for autophagy, which contributed to the enhanced anti-bacterial immunity. We showed that autophagy-related protein 2 (atg-2) that is upregulated by HLH-30/TFEB, mediated increased immunity in male animals. Thus, male C. elegans appear to be equipped with enhanced autophagy for increasing pathogen resistance, likely conferring prolonged mate search with less infection.
2024-08-22 | GSE245430 | GEO