• Similar to NRF2, it is responsive to oxidative stress and activates antioxidant responsive element- (ARE-) driven genes [ 4 ]. (hindawi.com)
  • Single cells and organisms may adapt to harmful oxidative stress conditions, through stress-activated factors. (springer.com)
  • Protection against chromium (VI)-induced oxidative stress and apoptosis by Nrf2. (cdc.gov)
  • Nrf2, an antioxidant-activated cap 'n' collar bZip transcription factor, has recently emerged as a critical regulator of cellular defense against oxidative stress, a prominent component in the pathogenesis of a broad range of disease and chemical toxicity including metal-induced cancer and toxicity. (cdc.gov)
  • Taken together, these findings suggest that PQS could effectively inhibit VSMCs calcification by ameliorating oxidative stress and regulating osteogenic genes via the promotion of Nrf2 expression. (biomedcentral.com)
  • Nrf2 expression is stimulated by oxidative stress, electrophiles and chemical activators (PMID: 25761198, PMID: 27638861 and PMID: 28587109). (abcam.com)
  • Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:11035812, PubMed:19489739, PubMed:29018201, PubMed:31398338). (bicnirrh.res.in)
  • In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:19489739, PubMed:29590092). (bicnirrh.res.in)
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
  • Under normal conditions, Keap1 promotes ubiquitination and eventual degradation of Nrf2. (springer.com)
  • Cr(VI) at a non-toxic concentration activates Nrf2 by interacting with critical cysteine residues of Nrf2 and Keap1--a cytoplasmic Nrf2-binding partner that controls the degradation of Nrf2 in the absence of an inducer. (cdc.gov)
  • The mRNA and protein expression levels of Nrf2, the antioxidant gene heme oxygenase-1 (HO-1), osteogenic markers, including runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and Kelch-like ECH-associated protein 1 (Keap1) were also measured. (biomedcentral.com)
  • PQS suppressed the Pi-induced protein expression of Keap1, which is an endogenous inhibitor of Nrf2. (biomedcentral.com)
  • Keap1 siRNA treatment induced Nrf2 expression and downregulated Runx2 expression in the presence of Pi and PQS. (biomedcentral.com)
  • The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20452972). (bicnirrh.res.in)
  • Both, NRF1 and NRF2 reside outside of the nucleus under unstressed conditions: NRF1 in the endoplasmic reticulum (ER) and NRF2 in the cytoplasm [ 5 ]. (hindawi.com)
  • Three arms exist in the ER stress response: the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) pathways, where each of the sensor proteins is a membrane protein ( Figure 1 ). (encyclopedia.pub)
  • It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). (cancerindex.org)
  • The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc. (cancerindex.org)
  • Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. (cancerindex.org)
  • The prognostic significance of the major redox regulator nuclear factor erythroid-2-related factor (NRF2) is recognized in many cancers, but the role of NRF1 is not generally well understood in cancer. (hindawi.com)
  • Nuclear factor erythroid-2-related factor 2 (NRF2) is the most studied member of the Cap 'n' collar basic leucine zipper (CNC-bZIP) family of transcription factors. (hindawi.com)
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
  • Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. (wikipedia.org)
  • The intracellular reactive oxygen species (ROS) levels and the transcriptional activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined. (biomedcentral.com)
  • OBJECTIVE- Sulforaphane is an activator of transcription factor NF-E2-related factor-2 (nrf2) that regulates gene expression through the promoter antioxidant response element (ARE). (diabetesjournals.org)
  • Nrf2 regulates the transcription of a battery of protective and metabolic enzymes. (diabetesjournals.org)
  • a novel cascade mediated by AP-1 and FOXF1 that regulates oncogene-induced senescence, is reported. (cusabio.com)
  • This gene encodes a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. (cancerindex.org)
  • The ISR (Fig. 1 ) is a complex signaling pathway that regulates cellular responses to stress stimuli and enables either adaptation or the instigation of cell death mechanisms [ 2 ]. (biomedcentral.com)
  • IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. (cancerindex.org)
  • The integrated stress response is a signaling pathway activated in cancer cells in response to both dysregulated growth and metabolism, and also following exposure to many therapies that appears one such targetable pathway for improved treatment of these diseases. (biomedcentral.com)
  • Nrf2 stabilization and increase in its half-life even to 200 min [ 9 ] allows nuclear translocation and activation of transcription of cytoprotective genes (Fig. 1 ). (springer.com)
  • Activated Nrf2 mediates induction of a battery of cytoprotective genes encoding phase 2 detoxification enzymes and antioxidative proteins that inhibit ROS production and apoptosis by Cr(VI). (cdc.gov)
  • PQS treatment reduced intracellular ROS production and significantly upregulated Nrf2 transcriptional activity and the expression of Nrf2 and its target antioxidant gene HO-1. (biomedcentral.com)
  • Given that OKSM (Yamanaka) factors convert somatic cells into induced pluripotent stem (iPS) cells, alterations in transcriptional state could affect destiny of the cells. (intechopen.com)
  • Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. (cusabio.com)
  • In addition, NRF1 and NRF2 mRNA and miR-23B, miR-93, miR-144, miR-212, miR-340, miR-383, and miR-510 levels were analysed with real-time qPCR from 54 paraffin-embedded naevi and melanoma samples. (hindawi.com)
  • Furthermore, the miRNAs correlated negatively with the immunohistochemical expression of NRF1 and NRF2 but positively with their respective mRNA. (hindawi.com)
  • The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor. (cancerindex.org)
  • The isoform encoded by the unspliced mRNA, XBP1(U), is constitutively expressed, and thought to function as a negative feedback regulator of XBP1(S), which shuts off transcription of target genes during the recovery phase of ER stress. (cancerindex.org)
  • We characterized the immunohistochemical expression of NRF1 and NRF2 in 99 naevi, 88 primary skin melanomas, and 67 lymph node metastases. (hindawi.com)
  • From the same family of transcription factors, NRF1 is generally far less studied and its role in carcinogenesis is insufficiently explored. (hindawi.com)
  • Several events contribute to NRF1 and NRF2 activation, among them the proteolytic cleavage of NRF1 from the ER membrane and the phosphorylation of NRF2. (hindawi.com)
  • In particular, miR-23B, miR-93, miR-144, and miR-212 were found to play a role as NRF2 inhibitors, while miR-340 appears to have a role as an NRF1 and MAPK inhibitor with miR-383 and miR-510 having a less clear role in the regulation of NRF1 and NRF2 levels [ 7 ]. (hindawi.com)
  • Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1). (wikipedia.org)
  • Targeted disruption or siRNA-mediated knockdown of Nrf2 markedly elevated ROS production under basal conditions and in the presence of Cr(VI) that involves altered oxygen and energy metabolism in the mitochondria. (cdc.gov)
  • ROS formation was increased further by knockdown of nrf2 and transketolase expression. (diabetesjournals.org)
  • NRF2 is bound to ubiquitin when it is the nucleus so MW would be higher than cytoplasm. (abcam.com)
  • RESULTS- Activation of nrf2 by sulforaphane induced nuclear translocation of nrf2 and increased ARE-linked gene expression, for example, three- to fivefold increased expression of transketolase and glutathione reductase. (diabetesjournals.org)
  • The JUN protein is a transcription factor that plays a crucial role in regulating gene expression in response to a variety of signals, including growth factors, cytokines, and stress. (cusabio.com)
  • encoded by Nfe2l2 gene) is a transcription factor responsible for the regulation of cellular redox balance and protective antioxidant and phase II detoxification responses in mammals [ 1 , 2 ]. (springer.com)
  • Nrf2 is a master eukaryotic redox-active factor and belongs to Cap 'n' Collar (Cnc)-bZIP (basic leucine zipper) family of transcription factors. (springer.com)
  • PERK, (a component of the integrated stress response) then phosphorylates the eukaryotic translation initiation factor 2 subunit −α (eIF2α), which results in global translational arrest. (encyclopedia.pub)
  • The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
  • We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in NSCLC. (oncotarget.com)
  • Immunohistochemistry was performed to detect Nrf2 or NQO1 expression. (oncotarget.com)
  • The correlation between Nrf2 or NQO1 expression and survival outcomes was evaluated using the Kaplan-Meier method and Cox proportional hazards regression model. (oncotarget.com)
  • Levels of Nrf2 and NQO1 were elevated in tumor tissues. (oncotarget.com)
  • NQO1 expression positively correlated with Nrf2 expression ( P = 0.039). (oncotarget.com)
  • As compared with either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more predictive of superior overall survival ( P = 0.020) and disease free survival ( P = 0.037). (oncotarget.com)
  • Subgroup analyses showed that females, nonsmokers, and patients with advanced-stage NSCLC were suitable populations in which to evaluate prognosis based on Nrf2 and NQO1 co-expression. (oncotarget.com)
  • These results indicate that dual-negative expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC patients. (oncotarget.com)
  • Nrf2 expression positively correlated with lymph node metastasis ( P = 0.001) and negatively correlated with tumor differentiation ( P = 0.032). (oncotarget.com)
  • In addition, the subcellular distribution of mitochondria can affect the cellular transcriptome and transcription rates. (hindawi.com)
  • It is a main inductor of genes of antioxidant proteins and phase II detoxifying enzymes [ 1 ]. (hindawi.com)
  • The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
  • This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. (bicnirrh.res.in)
  • This was associated with DIM‐enhanced phosphorylation of the signaling intermediates Akt, insulin receptor substrate‐1, and insulin receptor early in differentiation. (researchgate.net)
  • Nrf2 antibody (ab137550) detects no signal in most untreated samples for WB. (abcam.com)
  • Then primary antibody (1% BSA) was incubated at 4°C overnight. (cusabio.com)
  • The cDNA synthesized by RNA reverse transcription is then used as a template for PCR amplification of the JUN antibody gene. (cusabio.com)
  • The mammalian ER stress response consists of three arms: the inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR)-like ER kinase (PERK), and activating transcription factor 6 (ATF6) pathways. (encyclopedia.pub)
  • First, the general TFs (GTFs), including preinitiation complex components TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and THIIH, are the primary protein factors that are required for the initiation of transcription from the TATA box (or TATA element), then elongation is executed by RNA polymerase II (RNA pol II) [ 1 ]. (intechopen.com)
  • it results from expansion of polyglutamine repeats in the protein huntingtin [ 1 ] . (encyclopedia.pub)
  • Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
  • This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. (cancerindex.org)
  • NFE2L1 is a cap 'n' collar, basic-leucine zipper (bZIP) transcription factor. (wikipedia.org)
  • NF-E2-related factor 2 (Nrf2) is a member of the Cap'n'Collar/basic leucine zipper (CNC-bZIP) transcription factor family. (oncotarget.com)
  • It forms homodimers or heterodimers with other transcription factors, such as FOS, to bind to specific DNA sequences known as AP-1 sites in the promoter regions of target genes. (cusabio.com)
  • Nrf2 potentially coordinate a network of protective mechanisms against mitochondrial damage by toxic metals. (cdc.gov)
  • As a consequence, both factors are transported to the nucleus to induce the expression of their target genes. (hindawi.com)
  • NFE2L1 was shown to directly bind and activate expression of the PsmB6 gene, which encodes a catalytic subunit of the 20S core. (wikipedia.org)
  • For example, hydrogen peroxide (H 2 O 2 ) is a classic oxidant stressor that promotes vascular cell calcification by increasing the expression of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) [ 11 ]. (biomedcentral.com)
  • This also abolished the counteracting effect of sulforaphane, suggesting mediation by nrf2 and related increase of transketolase expression. (diabetesjournals.org)
  • CONCLUSIONS- We conclude that activation of nrf2 may prevent biochemical dysfunction and related functional responses of endothelial cells induced by hyperglycemia in which increased expression of transketolase has a pivotal role. (diabetesjournals.org)
  • Recombinant fragment corresponding to Human Nrf2 aa 108-413 (internal sequence). (abcam.com)
  • HO-1 and their products exert beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. (springer.com)
  • The aim of this study was to assess whether activation of nrf2 by sulforaphane in human microvascular endothelial cells prevents metabolic dysfunction in hyperglycemia. (diabetesjournals.org)
  • Failure of the PN is associated with broad range of diseases including cancer, neurodegeneration, and immunological and metabolic disorders [ 1 ]. (hindawi.com)
  • Type 1 diabetes mellitus is a metabolic disease resulting from the destruction of insulinproducing β cells in the pancreas, that leads to hyperglycemia [1,2,20]. (researchgate.net)
  • Once bound, JUN can either activate or repress the transcription of these genes, depending on the context and the presence of other cofactors. (cusabio.com)
  • This activates cascade of events which, in the end, affects oxidative status of the cells and provides robust protection against oxidative challenge. (springer.com)
  • Functional studies in non-small cell lung cancer (NSCLC) patients revealed that hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor growth. (oncotarget.com)
  • In particular, Nrf2 was elevated in nearly all tumor cells. (oncotarget.com)
  • However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. (bvsalud.org)
  • Data demonstrated that Nrf2 is critically involved in the cellular response to Cr(VI)-induced ROS production and cell death. (cdc.gov)
  • The vertical axis represents relative risk, level of probable pathological organism response where normal level is 1. (anti-agingfirewalls.com)
  • However, the 5-year survival of NSCLC patients is still as low as 15% [ 1 ]. (oncotarget.com)
  • Together, this data sheds new light about NFE2L family factors in pigment tumors and suggests that these factors are worth for further explorations. (hindawi.com)
  • 2012) MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function and pathogenicity of Magnaporthe oryzae. (prelekara.sk)
  • Molecular mechanisms of the initiation of transcription from TATA box have been well known as the most essential nuclear events in mammalian cells. (intechopen.com)
  • Progress in genetic analyses have advanced our understanding of the molecular drivers underpinning hematologic malignancies, thus prompting the development of an array of targeted therapies that are revolutionizing the clinical management of these diseases [ 1 ]. (biomedcentral.com)
  • Metallothioenein-1 and Metallothioenein-2 genes, which protect cells against cytotoxicity induced by toxic metals, are also direct targets of Nfe2l1. (wikipedia.org)
  • RESEARCH DESIGN AND METHODS- Human microvascular HMEC-1 endothelial cells were incubated in low and high glucose concentrations (5 and 30 mmol/l, respectively), and activation of nrf2 was assessed by nuclear translocation. (diabetesjournals.org)
  • Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. (bvsalud.org)