ArticleMolecular and cellular biology2013
The casein kinase 2-nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 60 citations in OpenAlex.
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- scBSP: A fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data.bioRxiv : the preprint server for biology · 2025Article
- 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
- The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis.Scientific reports · 2023Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- The Nrf1 transcription factor is induced by patulin and protects against patulin cytotoxicity.Toxicology · 2022Article
- Okur-Chung neurodevelopmental syndrome-linked CK2α variants have reduced kinase activity.Human genetics · 2021Article
- A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3.Biochemistry. Biokhimiia · 2021Review
- Trash Talk: Mammalian Proteasome Regulation at the Transcriptional Level.Trends in genetics : TIG · 2021Review
- Review
- Roles of NRF3 in the Hallmarks of Cancer: Proteasomal Inactivation of Tumor Suppressors.Cancers · 2020Review
- Regulation of NRF1, a master transcription factor of proteasome genes: implications for cancer and neurodegeneration.Molecular biology of the cell · 2020Article
- Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.International journal of molecular sciences · 2020Review
- NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression.Molecular and cellular biology · 2020Article
- ER-Resident Transcription Factor Nrf1 Regulates Proteasome Expression and Beyond.International journal of molecular sciences · 2020Review
- NRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma Protein.Molecular and cellular biology · 2020Article
- New addiction to the NRF2-related factor NRF3 in cancer cells: Ubiquitin-independent proteolysis through the 20S proteasome.Cancer science · 2020Review
- β-Catenin/TCF4 Complex-Mediated Induction of theInternational journal of molecular sciences · 2019Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impairment of the ubiquitin-proteasome system (UPS) has been implicated in the pathogenesis of human diseases, including neurodegenerative disorders. Thus, stimulating proteasome activity is a promising strategy to ameliorate these age-related diseases. Here we show that the protein kinase casein kinase 2 (CK2) regulates the transcriptional activity of Nrf1 to control the expression of the proteasome genes and thus the clearance of ubiquitinated proteins. We identify CK2 as an Nrf1-binding protein and find that the knockdown of CK2 enhances the Nrf1-dependent expression of the proteasome subunit genes. Real-time monitoring of proteasome activity reveals that CK2 knockdown alleviates the accumulation of ubiquitinated proteins upon proteasome inhibition. Furthermore, we identify Ser 497 of Nrf1 as the CK2 phosphorylation site and demonstrate that its alanine substitution (S497A) augments the transcriptional activity of Nrf1 and mitigates proteasome dysfunction and the formation of p62-positive juxtanuclear inclusion bodies upon proteasome inhibition. These results indicate that the CK2-mediated phosphorylation of Nrf1 suppresses the proteasome gene expression and activity and thus suggest that the CK2-Nrf1 axis is a potential therapeutic target for diseases associated with UPS impairment.
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