TFEB and TFE3 are novel components of the integrated stress response

To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Autophagy & Cell Death, Membrane & Intracellular Transport, Transcription Articles Source Type: research

Related Links:

ConclusionsIn skeletal muscle, GSK-3β inactivation causes dephosphorylation and nuclear translocation of TFEB resulting in TFEB-dependent induction of Pgc-1α expression.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research
Publication date: Available online 14 November 2019Source: Life SciencesAuthor(s): Wanli Ji, Kun Liang, Rui An, Xinhong WangAbstractAimsCurrently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastri...
Source: Life Sciences - Category: Biology Source Type: research
In this report, a novel CypA gene from sea cucumber Apostichopus japonicus (designated as AjCypA) was cloned and its function roles in immune responses were explored. The full-length cDNA of AjCypA was 1297 bp containing an open reading frame of 489 bp encoding a putative protein of 162 amino acids (aa). A conserved cyclophilin-like domain (CLD) with PPIase signature was located from 5 to 155 aa sequences in AjCypA, in which five necessary aa residues was totally conserved. In healthy sea cucumbers, AjCypA was expressed in all detected tissues, with highly expressed in muscles and weakly expressed in coelomocytes. AjCypA t...
Source: Fish and Shellfish Immunology - Category: Biology Source Type: research
Publication date: Available online 1 November 2019Source: European Polymer JournalAuthor(s): Chang-Hui Wang, Meng-Bo Luo, Xiaojun Xu, Chao Wang, Li-Zhen SunAbstractThe salt concentration-dependent polyelectrolyte translocation through a cylinder nanopore is studied using Langevin dynamics simulation. We use the Debye-Hückel model combined with the generalized Born model to account for the salt-induced screening effect and the polarization effect for the polyelectrolyte charges. We prove the validity of our simulation model through the extensive simulation-experiment comparisons for the polyelectrolyte statistical size...
Source: European Polymer Journal - Category: Chemistry Source Type: research
AbstractAmyotrophic Lateral Sclerosis (ALS), a debilitating neurodegenerative disorder is related to mutations in a number of genes, and certain genes of the Ribonuclease (RNASE) superfamily trigger ALS more frequently. Even though missense mutations in Angiogenin (ANG) and Ribonuclease 4 (RNASE4) have been previously shown to cause ALS through loss-of-function mechanisms, understanding the role of rare variants with a plausible explanation of their functional loss mechanisms is an important mission. The study aims to understand if any of the rare ANG and RNASE4 variants catalogued in Project MinE consortium caused ALS due...
Source: Metabolic Brain Disease - Category: Neurology Source Type: research
;n CG Abstract Bifidobacterium animalis subsp. lactis IPLA 20020 and Lactobacillus gasseri IPLA 20212, two strains isolated from human samples, were evaluated for safety and influence over the intestinal microbiota and cytokine production by the intestinal tissue of adult BALB/c mice. Mice were divided into four groups receiving during 8 days PBS or a suspension of each strain, prepared fresh or lyophilized (bifidobacteria), at an amount of 4x108 viable cells/day. This dose could be comparable to the probiotic intake of a human adult who consumed about 100-200 mL of functional fermented milk per day, considering t...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Publication date: Available online 14 November 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Atanu Banerjee, Alexis Moreno, Mohammad Firoz Khan, Remya Nair, Suman Sharma, Sobhan Sen, Alok Kumar Mondal, Jorgaq Pata, Cédric Orelle, Pierre Falson, Rajendra PrasadAbstractATP-binding cassette (ABC) transporters couple ATP binding and hydrolysis to the translocation of allocrites across membranes. Two shared nucleotide-binding sites (NBS) participate in this cycle. In asymmetric ABC pumps, only one of them hydrolyzes ATP, and the functional role of the other remains unclear. Using a drug-based s...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research
In this study, we showed that Linagliptin had a protective role in AGEs-induced chondrocyte injury. The presence of Linagliptin ameliorated AGEs-induced reactive oxygen species (ROS) induction and reduced cellular protein carboxyl content. Linagliptin mitigated AGEs-induced mitochondrial membrane potential (ΔΨm) reduction and NAPDH oxidase subunit NOX-4 induction, indicating that Linagliptin is a potent anti-ROS agent in chondrocytes. Additionally, Linagliptin inhibited AGEs-induced production of high mobility group box chromosomal protein 1 (HMGB-1), and the expression of matrix metalloproteases (MMPs)-2 and &mi...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
AbstractFollowing peripheral nerve injury, remnant Schwann cells adopt a migratory phenotype and remodel the extracellular matrix allowing axonal regrowth. Although much evidence has demonstrated that TGF ‐β1 promotes glioma cell motility and induces the expression of extracellular matrix proteins, the effects of TGF‐β1 on Schwann cell migration has not yet been studied. We therefore investigated the cellular effects and the signal transduction pathways evoked by TGF‐β1 inrattus norvegicus neuronal Schwann RSC96 cell. TGF ‐β1 significantly increased migration and invasion of Schwann cells assess...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage.
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
More News: Genetics | Molecular Biology | Translocation