ArticleThe Journal of biological chemistry2019
Nrf1-mediated transcriptional regulation of the proteasome requires a functional TIP60 complex.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The ubiquitin-proteasome system is an important driver of EBV-associated nasopharyngeal carcinoma progression: a meta-analysis of transcriptomic data.Scientific reports · 2026Pooled it
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.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
- Anthracyclines attenuate Nrf1-dependent proteolytic pathways and potentiate proteasome inhibitor cytotoxicity.Molecular biology of the cell · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Ferroptosis regulation by Cap'n'collar family transcription factors.The Journal of biological chemistry · 2024Review
- Transcription factor Nrf1 regulates proteotoxic stress-induced autophagy.The Journal of cell biology · 2024Article
- Evaluation of the NRF1-proteasome axis as a therapeutic target in breast cancer.Scientific reports · 2023Article
- Itraconazole Confers Cytoprotection Against Neurodegenerative Disease-Associated Abnormal Protein Aggregation.Molecular neurobiology · 2023Article
- Metabolic signature and proteasome activity controls synovial migration ofFrontiers in immunology · 2023Article
- Review
- Regulation of NRF1, a master transcription factor of proteasome genes: implications for cancer and neurodegeneration.Molecular biology of the cell · 2020Article
- Proteotoxic Stress and Cell Death in Cancer Cells.Cancers · 2020Review
- ER-Resident Transcription Factor Nrf1 Regulates Proteasome Expression and Beyond.International journal of molecular sciences · 2020Review
- Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma.Cancers · 2020Article
- BET Inhibitors Synergize with Carfilzomib to Induce Cell Death in Cancer Cells via Impairing Nrf1 Transcriptional Activity and Exacerbating the Unfolded Protein Response.Biomolecules · 2020Article
- Long isoforms of NRF1 negatively regulate adipogenesis via suppression of PPARγ expression.Redox biology · 2020Article
- Disabling the Protease DDI2 Attenuates the Transcriptional Activity of NRF1 and Potentiates Proteasome Inhibitor Cytotoxicity.International journal of molecular sciences · 2020Article
- Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.Frontiers in molecular biosciences · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Inhibition of the proteasome leads to proteotoxic stress, which is characterized by the buildup of ubiquitinated proteins that cannot be degraded properly. The transcription factor Nrf1 (also called NFE2L1) counteracts proteotoxic stress by inducing transcription of proteasome subunit genes, resulting in the restoration of proteasome activity. Further understanding of the Nrf1 pathway is therefore of interest in both neurodegeneration, where proteasome activity could be enhanced, and cancer, where suppression of this pathway could potentiate the cell-killing effect mediated by proteasome inhibitor drugs. Here, to identify novel regulators of Nrf1, we performed an RNAi screen in an engineered cell line, reporting on Nrf1 transcriptional activity. In addition to validating known regulators, we discovered that the AAA+ ATPase RUVBL1 is necessary for Nrf1's transcriptional activity. Given that RUVBL1 is part of different multisubunit complexes that play key roles in transcription, we dissected this phenomenon further and found that the TIP60 chromatin-regulatory complex is essential for Nrf1-dependent transcription of proteasome genes. Consistent with these observations, Nrf1, RUVBL1, and TIP60 proteins were co-recruited to the promoter regions of proteasome genes after proteasome inhibitor treatments. More importantly, depletion of RUVBL1 or TIP60 in various cancer cells sensitized them to cell death induced by proteasome inhibition. Overall, our study provides a framework for manipulating the TIP60-Nrf1 axis to alter proteasome function in various human diseases, including cancer.
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Registered trials
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