ArticlePloS one2014
The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
- Ferroptosis regulation by Cap'n'collar family transcription factors.The Journal of biological chemistry · 2024Review
- Understanding the Transcription Factor NFE2L1/NRF1 from the Perspective of Hallmarks of Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- TCF11 Has a Potent Tumor-Repressing Effect Than Its Prototypic Nrf1α by Definition of Both Similar Yet Different Regulatory Profiles, With a Striking Disparity From Nrf2.Frontiers in oncology · 2021Article
- Natural Nrf2 Modulators for Skin Protection.Antioxidants (Basel, Switzerland) · 2020Review
- Overexpression ofInternational journal of molecular sciences · 2020Article
- Decreased levels of constitutive proteasomes in experimental autoimmune encephalomyelitis may be caused by a combination of subunit displacement and reduced Nfe2l1 expression.Journal of neurochemistry · 2020Article
- Distinct isoforms of Nrf1 diversely regulate different subsets of its cognate target genes.Scientific reports · 2019Article
- Article
- Nrf1D Is the First Candidate Secretory Transcription Factor in the Blood Plasma, Its Precursor Existing as a Unique Redox-Sensitive Transmembrane CNC-bZIP Protein in Hemopoietic and Somatic Tissues.International journal of molecular sciences · 2018Article
- Nach Is a Novel Subgroup at an Early Evolutionary Stage of the CNC-bZIP Subfamily Transcription Factors from the Marine Bacteria to Humans.International journal of molecular sciences · 2018Article
- Review
- TALENs-directed knockout of the full-length transcription factor Nrf1α that represses malignant behaviour of human hepatocellular carcinoma (HepG2) cells.Scientific reports · 2016Article
- The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression.Scientific reports · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.
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