Oxidation of multiple MiT/TFE transcription factors links oxidative stress to transcriptional control of autophagy and lysosome biogenesis.

Oxidation of multiple MiT/TFE transcription factors links oxidative stress to transcriptional control of autophagy and lysosome biogenesis. Autophagy. 2019 Dec 11;: Authors: Wang H, Wang N, Xu D, Ma Q, Chen Y, Xu S, Xia Q, Zhang Y, Prehn JHM, Wang G, Ying Z Abstract Significant evidences indicate that reactive oxygen species (ROS) can induce macroautophagy/autophagy under both physiological and pathological conditions. Although the relationship between ROS and autophagy regulation has been well studied, the basic mechanism by which ROS affects autophagy and the biological role of this regulation are still not fully understood. In the present study we show that multiple MiT-TFE transcription factors including TFEB, TFE3 and MITF, which are master regulators of autophagy and lysosomal biogenesis, can be activated upon direct cysteine oxidation by ROS. Oxidation promotes the nuclear translocation of these MiT-TFE transcription factors by inhibiting the association of them with RRAG GTPases, which in turn leads to enhanced global gene expression level in autophagy-lysosome system. Our study highlights the role of oxidation of MiT-TFE transcription factors in ROS-linked autophagy, and provides novel mechanism that MiT-TFE transcription factors-mediated transcriptional control of autophagy may govern cell homeostasis in response to oxidative stress, a biological process tightly linked to human diseases including neurodegenerative diseases and cancer. PMID...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research

Related Links:

Abstract In mammals, DNA methyltransferases transfer a methyl group from S-adenosylmethionine to the 5 position of cytosine in DNA. The product of this reaction, 5-methylcytosine (5mC), has many roles, particularly in suppressing transposable and repeat elements in DNA. Moreover, in many cellular systems, cell lineage specification is accompanied by DNA demethylation at the promoters of genes expressed at high levels in the differentiated cells. However, since direct cleavage of the C-C bond connecting the methyl group to the 5 position of cytosine is thermodynamically disfavoured, the question of whether DNA meth...
Source: Journal of Biosciences - Category: Biomedical Science Authors: Tags: J Biosci Source Type: research
Authors: Wu J, Li YT, Tian XT, Liu YS, Wu ML, Li PN, Liu J Abstract BACKGROUNDS: Anaplastic thyroid cancer/ATC is highly lethal malignancy without reliable chemotherapeutic drug. Resveratrol possesses anti-ATC activities but encounters resistance in some cases due to certain unknown reason(s). OBJECTIVE: Because signal transducer and activator of transcription/STAT3 signaling is critical for ATC cell survival and the main molecular target of resveratrol, its roles in determining the fates of resveratrol-treated ATC cells were investigated here. METHODS: Human THJ-11T, THJ-16 and THJ-21T ATC cell lines were ...
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
CONCLUSIONS: LncRNA SNHG20 promotes the proliferation and inhibits the apoptosis of NSCLC cells by targeting miR-197 through the Wnt/β-catenin signaling pathway. PMID: 31957836 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL-induced osteoclast formation and resorbed pits of hydroxyapatite-coated plate in a dose-dependent manner. D.P also disrupted the formation of intact actin-rich podosome structures in mature osteoclasts and inhibited osteoclast-specific gene and protein expressions. Further, D.P was able to suppress RANKL-activated JNK, NF-κB and Ca2+ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential th...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Identification of a new cryptic PML-RARα fusion gene without t(15;17) and biallelic CEBPA mutation in a case of acute promyelocytic leukemia: a case detected only by RT-PCR but not cytogenetics and FISH. Cancer Biol Ther. 2020 Jan 20;:1-6 Authors: Zhang Z, Xu Y, Jiang M, Kong F, Chen Z, Liu S, Li F Abstract Acute promyelocytic leukemia (APL) is characterized by the presence of promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, which is formed following the specific chromosomal translocation t(15;17)(q22;q21). However, cases with PML-RARα generated by occult...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
e;n D, Bajory Z, Kulka J, Iványi B Abstract Xp11.2 translocation carcinoma is a distinct subtype of renal cell carcinoma characterized by translocations involving the TFE3 gene. Our study included the morphological, immunohistochemical and clinicopathological examination of 28 Xp11.2 RCCs. The immunophenotype has been assessed by using CA9, CK7, CD10, AMACR, MelanA, HMB45, Cathepsin K and TFE3 immunostainings. The diagnosis was confirmed by TFE3 break-apart FISH in 25 cases. The ages of 13 male and 15 female patients, without underlying renal disease or having undergone chemotherapy ranged from 8 to 72. The...
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
Conclusion: ATLIII has shown significant efficacy to inhibit IFN-γ-triggered Jak3/Stat3 pathway-dependent IDO activation, and do so through a direct binding to Jak3 protein. This study elucidated a new mechanism for the anticancer effect of ATLIII, which may provide a feasible target for the clinical immunotherapy of malignant tumors.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-κB (NF-κB) and mitogen-activated prot...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we have evaluated the role of α-lipoic acid in preventing the radiation-induced EMT and in sensitizing the breast cancer cells to radiation. The breast cancer cell lines, MCF-7 and MDA-MB-231 were pretreated with lipoic acid, irradiated and the changes associated with cell growth, clonogenicity, migration, matrix metalloproteinases (MMPs), EMT and TGFβ signaling were measured. Our data showed that lipoic acid pretreatment sensitized the breast cancer cells to the ionizing radiation and inhibited the radiation-induced migration and the release of MMP2 and MMP9. Lipoic acid also prevented the TGF&be...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Publication date: Available online 15 January 2020Source: Life SciencesAuthor(s): Zhi Zeng, Zi-yao Wang, Yu-kun Li, Dong-mei Ye, Juan Zeng, Jia-li Hu, Pi-feng Chen, Jiao Xiao, Juan Zou, Zhen-hua LiAbstractNuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development...
Source: Life Sciences - Category: Biology Source Type: research
More News: Brain | Cancer | Cancer & Oncology | Cytology | Genetics | Neurology | Study | Translocation