OverexpressionTranslocation of TFEB into the nucleusGenesPathwayPhosphorylationNuclearMTORC1ActivationBiogenesis and autophagyCytosolLysosomal storage dTranscription factorsTFE3UpregulationRegulationGenePromotesRegulatorProteinRenalNucleusFLCNAxisActivatesOxidativeTranscriptionalInductionMacrophagesMiceFunctionalTherapeuticEffectMarkersExpression
Overexpression12
- TFEB overexpression in cultured cells induces lysosomal biogenesis, exocytosis and autophagy. (wikipedia.org)
- Viral-mediated TFEB overexpression in cellular and mouse models of lysosomal storage disorders and in common neurodegenerative diseases such as Huntington, Parkinson and Alzheimer diseases, resulted in intracellular clearance of accumulating molecules and rescue of disease phenotypes. (wikipedia.org)
- TFEB overexpression has been found in patients with renal cell carcinoma and pancreatic cancer and was shown to promote tumorogenesis via induction of various oncogenic signals. (wikipedia.org)
- Importantly, TFEB overexpression resulted in more nuclear TFEB and rescued cardiomyopathy phenotypes. (elsevierpure.com)
- A primary pathological step of RagC S75Y cardiomyopathy is defective mTOR-TFEB signaling, which can be corrected by TFEB overexpression, but not mTOR inhibition. (elsevierpure.com)
- Overexpression of TFEB activated autophagy and attenuated H 2 O 2 -induced ROS accumulation. (illinois.edu)
- Furthermore, TFEB overexpression attenuated H 2 O 2 -induced apoptosis by downregulating the caspase apoptotic pathway. (illinois.edu)
- We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (TFEB) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. (unina.it)
- These results show that TFEB overexpression and modulation of autophagy result in improvements of muscle pathology and of functional performance in the PD murine model, with delayed disease progression. (unina.it)
- The transcription factor EB (TFEB) promotes protein degradation by the autophagy and lysosomal pathway (ALP) and overexpression of TFEB was suggested for the treatment of ALP-related diseases that often affect the heart. (mdc-berlin.de)
- Cardiomyocyte-specific TFEB-overexpression promoted ALP gene expression during TAC, which was associated with heart failure. (mdc-berlin.de)
- Treatment of ALP-related diseases by overexpression of TFEB warrants careful consideration. (mdc-berlin.de)
Translocation of TFEB into the nucleus2
- Furthermore, H 2 O 2 treatment triggered the translocation of TFEB into the nucleus. (illinois.edu)
- Inactivation of mTORC1 in this pathway thus leads to translocation of TFEB into the nucleus, where it initiates autophagic and lysosomal-related gene expression. (mskcc.org)
Genes5
- Upon nutrient depletion and under aberrant lysosomal storage conditions such as in lysosomal storage diseases, TFEB translocates from the cytoplasm to the nucleus, resulting in the activation of its target genes. (wikipedia.org)
- Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature, which was almost completely abrogated by deletion of transcription factor hlh-30/TFEB , except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5 . (elifesciences.org)
- Upregulation of autophagy-related genes by increased TFEB dramatically enhanced autophagic activity and cell survival upon following a severe stressor. (elsevierpure.com)
- Morphological, histological, and real-time PCR analyses showed increased heart weights, exaggerated fibrosis, and higher expression of stress markers and remodeling genes in AAV9-Tfeb TAC compared to AAV9-Luc TAC. (mdc-berlin.de)
- Autophagy can further be regulated by several transcriptional factors such as NFkappaB and TFEB to promote expression of different autophagy genes and thus prolong autophagy activation ( 6 , 7 ). (frontiersin.org)
Pathway5
- We studied the effects of berberine on the NAD synthesis pathway and interactions between SIRT1 and TFEB. (physiciansweekly.com)
- We found that berberine promoted autophagy of peritoneal macrophages by activating SIRT1 via the NAD synthesis pathway and, in turn, promoting TFEB nuclear translocation and deacetylation. (physiciansweekly.com)
- This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1α in cells and conditional mice. (elsevierpure.com)
- Activation of the TFEB-lysosome pathway is important in regulating autophagy and apoptosis. (biomedcentral.com)
- Transcription factor EB (TFEB) has been shown to be the master regulatory of the autophagic-lysosomal pathway. (mskcc.org)
Phosphorylation5
- Nuclear localization and activity of TFEB is inhibited by serine phosphorylation by mTORC1 and extracellular signal-regulated kinase 2 (ERK2). (wikipedia.org)
- mTORC1 phosphorylation of TFEB occurs at the lysosomal surface, both of which are localized there by interaction with the Rag GTPases. (wikipedia.org)
- TFEB nuclear export is mediated by CRM1 and is dependent on phosphorylation. (wikipedia.org)
- A molecular description of this massive complex is helping us understand the regulation of the TFEB transcription factor and dependence of TFEB phosphorylation on FLCN and the RagC GDP state. (casmatx.com)
- The dual regulation of ERK and mTOR phosphorylation upstream of TFEB influences the death outcome of AML12 cells. (biomedcentral.com)
Nuclear5
- Nutrient depletion induces TFEB dephosphorylation and subsequent nuclear translocation via the phosphatase calcineurin. (wikipedia.org)
- AKT/PKB phosphorylates TFEB at serine 467 and inhibits TFEB nuclear translocation. (wikipedia.org)
- Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). (lu.se)
- However, mTOR inhibition failed to ameliorate cardiac phenotypes in the RagC S75Y cardiomyopathy models, concomitant with a failure to promote TFEB nuclear translocation. (elsevierpure.com)
- In cultured primary neurons from FTD-transgenic mice, synaptic stimulation inhibits MTORC1 signaling, thus promoting nuclear translocation of TFEB, which, in turn, induces clearance of MAPT/Tau oligomers. (elsevierpure.com)
MTORC13
- Pharmacological inhibition of AKT/PKB activates TFEB, promotes lysosome biogenesis and autophagy, and ameliorates neuropathology in mouse models of Juvenile Batten disease and Sanfilippo syndrome type B. TFEB is activated in Trex1-deficient cells via inhibition of mTORC1 activity, resulting in an expanded lysosomal compartment. (wikipedia.org)
- Further characterization identified aberrant mammalian target of rapamycin complex 1 (mTORC1) and transcription factor EB (TFEB) signaling, as well as metabolic abnormalities including dysregulated autophagy. (elsevierpure.com)
- Under normal conditions TFEB is phosphorylated by mTORC1 and remains in the cytoplasm. (mskcc.org)
Activation8
- In bacterial infection nicotinic acid adenine dinucleotide phosphate (NAADP) induction of lysosomal Ca2+ efflux and TFEB activation leads to enhanced expression of inflammatory cytokines. (wikipedia.org)
- TFEB constitutive activation, due to FLCN mutations, drives renal cystogenesis and tumorigenesis in Birt-Hogg-Dubé syndrome. (wikipedia.org)
- We also studied the effects of berberine-induced TFEB activation via SIRT1 on autophagy and apoptosis of peritoneal macrophages. (physiciansweekly.com)
- Conclusions: Our results indicate that activation of TFEB mediated autophagy alleviates H 2 O 2 -induced oxidative damage by reducing ROS accumulation and inhibiting caspase-dependent apoptosis. (illinois.edu)
- RNA-sequencing, real-time PCR and Western Blot revealed a stronger ALP activation in the hearts of AAV9-Tfeb TAC mice. (mdc-berlin.de)
- The Casma publication describes a novel mechanism to regulate TFEB activation without impacting the ability of mTOR to phosphorylate other targets involved in general cellular activity," said Andrea Ballabio, M.D. (casmatx.com)
- Conversely, synaptic activation fails to promote clearance of toxic MAPT/Tau in neurons expressing constitutively active RRAG GTPases, which sequester TFEB in the cytosol, or upon TFEB depletion. (elsevierpure.com)
- Activation of TFEB is also confirmed in vivo in DBS-stimulated AD mice. (elsevierpure.com)
Biogenesis and autophagy1
- We now provide evidence that TFEB (transcription factor EB), a master regulator of lysosomal biogenesis and autophagy, is a key mediator of this cellular response. (elsevierpure.com)
Cytosol2
- Phosphorylated TFEB is then retained in the cytosol by interaction with 14-3-3 proteins. (wikipedia.org)
- This observation was at least partially explained by increased and mTOR-independent physical interaction between RagC S75Y and TFEB in the cytosol. (elsevierpure.com)
Lysosomal storage d1
- TFEB regulates the levels of these enzymes, many of which are mutated in lysosomal storage disorders and neurodegeneration. (casmatx.com)
Transcription factors2
- Sirtuin deacetylase 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, activates several transcription factors, including TFEB. (physiciansweekly.com)
- Lysosomal biogenesis is regulated by transcription factors EB (TFEB) and E3 (TFE3), which are activated during starvation. (liu.se)
TFE31
- These translocations most commonly involve the TFE3 gene on locus Xp11.2 and less commonly involve the TFEB gene on locus 6p21. (medscape.com)
Upregulation1
Regulation5
- The functional regulation of SIRT1 and TFEB by berberine could be exploited as a potential therapeutic strategy for atherosclerosis. (physiciansweekly.com)
- These findings reveal an infection-specific host response to S. aureus , identify HLH-30/TFEB as its main regulator, reveal FMOs as important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α during S. aureus infection, with implications for host defense and inflammation in higher organisms. (elifesciences.org)
- The study titled, " GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis " discusses a newly identified molecular mechanism that demonstrates the role of GABARAP-dependent regulation of transcription factor EB (TFEB) during the onset of autophagy. (casmatx.com)
- Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. (elsevierpure.com)
- Role of TFEB-driven autophagy regulation in pancreatic cancer treatment. (uni-heidelberg.de)
Gene2
- Transcription factor EB is a protein that in humans is encoded by the TFEB gene. (wikipedia.org)
- TFEB is a master gene for lysosomal biogenesis. (wikipedia.org)
Promotes3
- TFEB is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington disease. (wikipedia.org)
- Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages. (physiciansweekly.com)
- Altogether our findings indicate that stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau. (elsevierpure.com)
Regulator3
- TFEB is the master regulator of lysosomal function and is required for maintaining cellular and whole-body health. (casmatx.com)
- While TFEB has been recognized as a promising therapeutic target, it is under the direct control of mechanistic target of rapamycin (mTOR), which is a central regulator of cellular homeostasis. (casmatx.com)
- Induction of autophagy is tightly regulated at the transcriptional level and involves the master regulator, transcription factor EB (TFEB). (biomedcentral.com)
Protein3
- TFEB is also a target of the protein kinase AKT/PKB. (wikipedia.org)
- Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. (lu.se)
- Knockdown of TFEB by siRNA reversed the effect of H 2 O 2 on protein abundance of LC3-II and p62 as well as the number of autophagosomes and autolysosomes. (illinois.edu)
Renal2
- Finally, the data illuminate TFEB as a potentially novel target for renal tubular stress resistance. (elsevierpure.com)
- TFEB rearranged renal cell carcinoma. (bvsalud.org)
Nucleus1
- A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. (ectsoc.org)
FLCN1
- The Science Advances paper concluded that the GABARAP-FLCN/FNIP-TFEB axis serves as a molecular sensor that regulates lysosomal homeostasis within the autophagy-lysosomal network. (casmatx.com)
Axis2
- Here, we demonstrate that the TP53/p53-FBXO22-TFEB (transcription factor EB) axis plays an essential role in this process through upregulating basal macroautophagy/autophagy. (elsevierpure.com)
- Taken together, these results suggest that TP53 upregulates basal autophagy through the FBXO22-TFEB axis, which governs the hormetic effect in chemotherapy. (elsevierpure.com)
Activates1
- The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. (umassmed.edu)
Oxidative4
- Transcription factor EB (TFEB)-mediated autophagy is an important cytoprotective mechanism against oxidative stress. (illinois.edu)
- However, effects of TFEB-mediated autophagy on the oxidative stress of bovine mammary epithelial cells remain unknown. (illinois.edu)
- Therefore, the main aim of the study was to investigate the role of TFEB-mediated autophagy in bovine mammary epithelial cells experiencing oxidative stress. (illinois.edu)
- Thus, TFEB-mediated autophagy in bovine mammary epithelial cells might play a positive role in response to oxidative stress. (biomedcentral.com)
Transcriptional1
- Mild stress-activated TP53 transcriptionally induced FBXO22, which in turn ubiquitinated KDM4B (lysine-specific demethylase 4B) complexed with MYC-NCOR1 suppressors for degradation, leading to transcriptional induction of TFEB. (elsevierpure.com)
Induction2
- However, TFEB-mediated ALP induction may perturb cardiac stress response. (mdc-berlin.de)
- Here, we report that PGC1α's induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. (elsevierpure.com)
Macrophages1
- A recently discovered transcription factor, transcription factor EB (TFEB) is known to activate autophagy in macrophages. (physiciansweekly.com)
Mice4
- We treated 1-month-old PD mice with an AAV2.9-MCK-TFEB vector. (unina.it)
- In muscles from TFEB-treated mice we observed reduced PAS staining and improved ultrastructure, with reduced number and increased translucency of lysosomes, while total glycogen content remained unchanged. (unina.it)
- We used adeno-associated viral vectors type 9 (AAV9) to overexpress TFEB (AAV9-Tfeb) or Luciferase-control (AAV9-Luc) in cardiomyocytes of 12-week-old male mice. (mdc-berlin.de)
- AAV9-Tfeb TAC mice showed a reduced LV ejection fraction and increased left ventricular diameters. (mdc-berlin.de)
Functional1
- Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD. (unina.it)
Therapeutic1
- TFEB has proven to be very beneficial in a variety of disease models and offers significant therapeutic potential. (casmatx.com)
Effect2
- Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). (lu.se)
- AAV9-Tfeb had no effect on cardiac structure and function in sham animals. (mdc-berlin.de)
Markers1
- TFEB, cathepsin K and melanocytic markers. (pathologyoutlines.com)