ArticleMolecular biology of the cell2020
Regulation of NRF1, a master transcription factor of proteasome genes: implications for cancer and neurodegeneration.
Article in Molecular biology of the cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Transcription Factors in the Pathogenesis of Schizophrenia.Life (Basel, Switzerland) · 2026Review
- Early proteasome downregulation and dysfunction drive proteostasis failure in Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Anthracyclines attenuate Nrf1-dependent proteolytic pathways and potentiate proteasome inhibitor cytotoxicity.Molecular biology of the cell · 2025Article
- Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease.Science advances · 2025Article
- Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.PLoS genetics · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Transcription factor Nrf1 regulates proteotoxic stress-induced autophagy.The Journal of cell biology · 2024Article
- An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.Science advances · 2023Article
- Physical Activity Rewires the Human Brain against Neurodegeneration.International journal of molecular sciences · 2022Article
- Identifying predictive signalling networks for Vedolizumab response in ulcerative colitis.International journal of colorectal disease · 2022Article
- Tsc2 knockout counteracts ubiquitin-proteasome system insufficiency and delays photoreceptor loss in retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Bortezomib-Encapsulated Dual Responsive Copolymeric Nanoparticles for Gallbladder Cancer Targeted Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- A Redox-Silent Analogue of Tocotrienol May Break the Homeostasis of Proteasomes in Human Malignant Mesothelioma Cells by Inhibiting STAT3 and NRF1.International journal of molecular sciences · 2022Article
- The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation.Biomolecules · 2021Review
- The Ubiquitin-Proteasome System in Immune Cells.Biomolecules · 2021Review
- Folding Mitochondrial-Mediated Cytosolic Proteostasis Into the Mitochondrial Unfolded Protein Response.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The ability to sense proteasome insufficiency and respond by directing the transcriptional synthesis of de novo proteasomes is a trait that is conserved in evolution and is found in organisms ranging from yeast to humans. This homeostatic mechanism in mammalian cells is driven by the transcription factor NRF1. Interestingly, NRF1 is synthesized as an endoplasmic reticulum (ER) membrane protein and when cellular proteasome activity is sufficient, it is retrotranslocated into the cytosol and targeted for destruction by the ER--associated degradation pathway (ERAD). However, when proteasome capacity is diminished, retrotranslocated NRF1 escapes ERAD and is activated into a mature transcription factor that traverses to the nucleus to induce proteasome genes. In this Perspective, we track the journey of NRF1 from the ER to the nucleus, with a special focus on the various molecular regulators it encounters along its way. Also, using human pathologies such as cancer and neurodegenerative diseases as examples, we explore the notion that modulating the NRF1-proteasome axis could provide the basis for a viable therapeutic strategy in these cases.
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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.