ArticleMolecular and cellular biology2011
Dual regulation of the transcriptional activity of Nrf1 by β-TrCP- and Hrd1-dependent degradation mechanisms.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 106 citations in OpenAlex.
- NRF1 is upregulated by docosahexaenoic acid to ameliorate MASH through the inhibition of ER stress.Cell death & disease · 2026Article
- NFE2L1/Nrf1 forms a coactivator complex post-peptide:Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein.Scientific reports · 2025Article
- Activating the NFE2L1-ubiquitin-proteasome system by DDI2 protects from ferroptosis.Cell death and differentiation · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
- Understanding the Transcription Factor NFE2L1/NRF1 from the Perspective of Hallmarks of Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024Article
- Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.Cell death & disease · 2024Article
- Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2.Science signaling · 2023Article
- Article
- The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis.Scientific reports · 2023Article
- Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- Keap1-Nrf2 Heterodimer: A Therapeutic Target to Ameliorate Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Review
- Trash Talk: Mammalian Proteasome Regulation at the Transcriptional Level.Trends in genetics : TIG · 2021Review
- The Dawn of Mitophagy: What Do We Know by Now?Current neuropharmacology · 2021Review
- Regulation of NRF1, a master transcription factor of proteasome genes: implications for cancer and neurodegeneration.Molecular biology of the cell · 2020Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A growing body of evidence suggests that Nrf1 is an inducible transcription factor that maintains cellular homeostasis. Under physiological conditions, Nrf1 is targeted to the endoplasmic reticulum (ER), implying that it translocates into the nucleus in response to an activating signal. However, the molecular mechanisms by which the function of Nrf1 is modulated remain poorly understood. Here, we report that two distinct degradation mechanisms regulate Nrf1 activity and the expression of its target genes. In the nucleus, β-TrCP, an adaptor for the SCF (Skp1-Cul1-F-box protein) ubiquitin ligase, promotes the degradation of Nrf1 by catalyzing its polyubiquitination. This activity requires a DSGLS motif on Nrf1, which is similar to the canonical β-TrCP recognition motif. The short interfering RNA (siRNA)-mediated silencing of β-TrCP markedly augments the expression of Nrf1 target genes, such as the proteasome subunit PSMC4, indicating that β-TrCP represses Nrf1 activation. Meanwhile, in the cytoplasm, Nrf1 is degraded and suppressed by the ER-associated degradation (ERAD) ubiquitin ligase Hrd1 and valosin-containing protein (VCP) under normal conditions. We identified a cytoplasmic degradation motif on Nrf1 between the NHB1 and NHB2 domains that exhibited species conservation. Thus, these results clearly suggest that both β-TrCP- and Hrd1-dependent degradation mechanisms regulate the transcriptional activity of Nrf1 to maintain cellular homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.