ArticleScientific reports2019
Disruption of CUL3-mediated ubiquitination causes proximal tubule injury and kidney fibrosis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Renal TRPM6 but not Kv1.1 is required for magnesium homeostasis in mice.American journal of physiology. Renal physiology · 2026Article
- GATA1 Transcriptionally Upregulates LMCD1, Promoting Ferroptosis in Sepsis-Associated Acute Kidney Injury Through the Hippo/YAP Pathway.The Kaohsiung journal of medical sciences · 2025Article
- Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- LncRNA XIST: A Breakthrough in Inflammation-related Diseases.Current medicinal chemistry · 2025Review
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.American journal of physiology. Renal physiology · 2024Article
- Post-translational modifications in kidney diseases and associated cardiovascular risk.Nature reviews. Nephrology · 2024Review
- Review
- Identification of novel biomarkers, shared molecular signatures and immune cell infiltration in heart and kidney failure by transcriptomics.Frontiers in immunology · 2024Article
- Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.American journal of physiology. Renal physiology · 2024Article
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Cullin 3 mutant causing familial hyperkalemic hypertension lacks normal activity in the kidney.American journal of physiology. Renal physiology · 2022Article
- COP9 signalosome deletion promotes renal injury and distal convoluted tubule remodeling.American journal of physiology. Renal physiology · 2022Article
- CUL3 and COPS5 Related to the Ubiquitin-Proteasome Pathway Are Potential Genes for Muscle Atrophy in Mice.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- NovelHypertension (Dallas, Tex. : 1979) · 2022Article
- Article
- Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure.Current hypertension reports · 2020Review
- The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation.Kidney international · 2020Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3 disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury. The cdk2-cyclin E inhibitor roscovitine did not prevent the effects of Cul3 deletion, but instead exacerbated the kidney injury. Injury occurred despite accumulation and activation of CUL3 substrate Keap1/Nrf2, proposed to be protective in kidney injury. Cul3 disruption led to progressive interstitial inflammation, functionally relevant renal fibrosis and death. Finally, we observed reduced CUL3 expression in several AKI and CKD mouse models and in fibrotic human kidney tissue. These data establish CUL3 knockout mice as a novel genetic CKD model in which dysregulation of the cell cycle may play a primary role in initiating tubule injury, and that CUL3 dysregulation could contribute to acute and fibrotic kidney disease.
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Registered trials
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