NFE2L1 Antibody
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Product Specs
Buffer
PBS with 0.02% Sodium Azide, 50% Glycerol, pH 7.3. Store at -20°C. Avoid freeze/thaw cycles.
Lead Time
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Synonyms
erythroid derived 2 antibody; like 1 antibody; Locus control region factor 1 antibody; Locus control region-factor 1 antibody; NF-E2-related factor 1 antibody; NF2L1_HUMAN antibody; NFE2 related factor 1 antibody; NFE2-related factor 1 antibody; NFE2L1 antibody; NRF1 antibody; Nuclear factor antibody; Nuclear Factor Erythroid 2 Related Factor 1 antibody; Nuclear factor erythroid 2-related factor 1 antibody; Nuclear factor erythroid derived 2 like 1 antibody; TCF-11 antibody; TCF11 antibody; Transcription factor 11 antibody; Transcription factor HBZ17 antibody; Transcription factor LCR F1 antibody; Transcription factor LCR-F1 antibody
Target Names
NFE2L1
Uniprot No.
Target Background
Function
NFE2L1 is an endoplasmic reticulum membrane sensor that translocates to the nucleus in response to various stresses, acting as a transcription factor. It is a precursor to the transcription factor NRF1. NFE2L1 can detect various cellular stresses, including cholesterol excess, oxidative stress, or proteasome inhibition. In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates to the nucleus to form the transcription factor NRF1.
NFE2L1 is a key sensor of cholesterol excess. In conditions of excessive cholesterol, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1. This allows for the expression of genes that promote cholesterol removal, such as CD36.
NFE2L1 is also involved in proteasome homeostasis. In response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus, and activates the expression of genes encoding proteasome subunits.
NFE2L1 is a CNC-type bZIP family transcription factor that translocates to the nucleus and regulates the expression of target genes in response to various stresses. It heterodimerizes with small-Maf proteins (MAFF, MAFG, or MAFK) and binds to DNA motifs, including the antioxidant response elements (AREs), which regulate the expression of genes involved in the oxidative stress response. NFE2L1 can either activate or repress the expression of target genes, depending on the specific context.
NFE2L1 plays a crucial role in cholesterol homeostasis by acting as a sensor of cholesterol excess. In low cholesterol conditions, NFE2L1 translocates to the nucleus and represses the expression of genes involved in defense against cholesterol excess, such as CD36. In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal.
NFE2L1 is critical for redox balance in response to oxidative stress. It binds to the AREs motifs on promoters and mediates the activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1, and MT2.
NFE2L1 plays an essential role during fetal liver hematopoiesis. It likely has a protective function against oxidative stress and is involved in lipid homeostasis in the liver.
NFE2L1 is also involved in proteasome homeostasis. In response to proteasome inhibition, it mediates the 'bounce-back' of proteasome subunits by translocating to the nucleus and activating the expression of genes encoding proteasome subunits. NFE2L1 also participates in regulating glucose flux.
Together with CEBPB, NFE2L1 represses the expression of DSPP during odontoblast differentiation. In response to ascorbic acid induction, it activates the expression of SP7/Osterix in osteoblasts.
Gene References Into Functions
- Data show that Nrf1 can adopt several topologies within membranes that are determined by its NTD. PMID: 20629635
- Fbw7 serves as a regulator of Nrf1 expression and reveals a novel function of Fbw7 in cellular stress response. PMID: 21953459
- Results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin PMID: 22500024
- Data indicate both Nrf1a and Nrf1b isoforms transcripts were detected in different mouse and human cell lines, and in various mouse tissues. PMID: 23144760
- Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1) cells. PMID: 24024152
- While Nrf2 is crucial for MRE/ARE-mediated transcription in response to copper, Nrf1 may activate MT-1 expression by a mechanism different from that Nrf2 employs. PMID: 24462598
- Nrf1 physically interacts with androgen receptor and enhances its DNA-binding activity, suggesting that the p65-Nrf1 isoform is a potential androgen receptor coactivator. PMID: 24466341
- The treatment with E2, Res, or VC significantly increased mRNA and protein expression levels of Nrf1. PMID: 25130429
- The results indicate that Nrf1 is a transcriptional activator of Herpud1 expression during ER stress, and they suggest Nrf1 is a key player in the regulation of the ER stress response in cells. PMID: 25637874
- This review outlines Nrf1 structure, function, regulation, and its links to insulin resistance, diabetes, and inflammation. PMID: 26254094
- Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors PMID: 26268886
- Together with molecular expression results, the authors thus suppose requirement of Nrf1alpha (and major derivates) for gene regulatory mechanisms repressing cancer cell process and malignant behaviour. PMID: 27065079
- These results uncover a new regulatory mechanism that USP15 activates Nrf1 against the beta-TrCP inhibition to maintain proteostasis. PMID: 27416755
- Here the authors show that the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is required to cleave and activate Nrf1. PMID: 27528193
- Nrf1 is regulated by O-GlcNAc transferase. PMID: 28625484
- Our investigation shows that the ER membrane protein TCF11/Nrf1 is an essential component of the cellular stress response mechanism. In response to cytotoxic stress, TCF11/Nrf1 is retrotranslocated and transferred to the nucleus where it induces proteasome subunit expression via binding to the ARE region of the relevant promoter. PMID: 27345029
- Data uncover an unexpected role for p97 in activation of transcription factor Nrf1 by relocalizing it from the endoplasmic reticulum lumen to the cytosol. PMID: 24448410
- Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations PMID: 26231763
- A proteasome inhibitor-stimulated Nrf1 protein-dependent compensatory increase in proteasome subunit gene expression reduces polycomb group protein level PMID: 22932898
- The study identifies casein kinase 2 as an NRF1-binding protein and finds that the knockdown of casein kinase 2 enhances the NRF1-dependent expression of the proteasome subunit genes. PMID: 23816881
- GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. PMID: 23623971
- Findings suggest that nuclear-related factor erythroid 2 transcription factor (Nrf1) may play a role in maintaining genomic integrity, and that Nrf1 dysregulation may induce tumorigenesis PMID: 22971132
- Data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing, and proteasomal-mediated degradation as well as by its phosphorylation status PMID: 22216197
- Report that proteasome inhibition can be anticipated by TCF11-dependent activation of human proteasome gene expression, which in turn is controlled by a HRD1-p97-ERAD feedback circle. PMID: 20932482
- Data show that nuclear factor erythroid-derived 2-related factor 1 (Nrf1), but not the related Nrf2, is necessary for induced proteasome gene transcription in mouse embryonic fibroblasts. PMID: 20385086
- A nuclear export signal (NES) localized in the N-terminus of TCF11 is responsible for the active nuclear export of the protein. PMID: 12729924
- p65Nrf1 has the potential to play an important role in modulating the response to oxidative stress by functioning as a transdominant repressor of Nrf2-mediated activation of ARE-dependent gene transcription PMID: 17609210
Database Links
Protein Families
BZIP family, CNC subfamily
Subcellular Location
[Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Endoplasmic reticulum membrane; Single-pass type III membrane protein.; [Transcription factor NRF1]: Nucleus.
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