ArticleJournal of cellular and molecular medicine2017
The activity of the carbamoyl phosphate synthase 1 promoter in human liver-derived cells is dependent on hepatocyte nuclear factor 3-beta.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- Datamining approaches for examining the low prevalence of N-acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes.Journal of inherited metabolic disease · 2024Article
- Article
- Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma.Scientific reports · 2023Article
- Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.Journal of clinical laboratory analysis · 2022Article
- Molecular Typing Based on Oxidative Stress Genes and Establishment of Prognostic Characteristics of 7 Genes in Lung Adenocarcinoma.Oxidative medicine and cellular longevity · 2022Article
- Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis.Oncology letters · 2021Article
- Key Enzymes in Pyrimidine Synthesis, CAD and CPS1, Predict Prognosis in Hepatocellular Carcinoma.Cancers · 2021Article
- CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020Review
- Article
- CRISPR/Cas9-based liver-derived reporter cells for screening of mPGES-1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells.Journal of cellular and molecular medicine · 2019Article
- Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment.World journal of stem cells · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbamoyl phosphate synthase 1 (CPS1) is the rate-limiting enzyme in the first step of the urea cycle and an indispensable enzyme in the metabolism of human liver. However, CPS1 epigenetic regulation involves promoter analysis and the role of liver-enriched transcription factors (LETFs), which is not fully elucidated. In this work, the promoter region of hCPS1 gene was cloned, and its activity was investigated. An LETF, hepatocyte nuclear factor 3-beta (HNF3β), was found to promote the transcriptional expression of CPS1 in liver-derived cell lines. In addition, dual-luciferase reporter assay shows that the essential binding sites of the HNF3β may exist in the oligonucleotide -70 nt to +73 nt. Two putative binding sites are available for HNF3β. Mutation analysis results show that the binding site 2 of HNF3β was effective, and the transcriptional activity of CPS1 promoter significantly decreased after mutation. Electrophoretic mobile shift assay (EMSA) and ChIP assay confirmed that HNF3β can interact with the binding site in the CPS1 promoter region of -70 nt to +73 nt promoter region in vivo and in vitro to regulate the transcription of CPS1. Moreover, HNF3β overexpression enhanced the transcription of CPS1 and consequently improved the mRNA and protein levels of CPS1, whereas the knockdown of HNF3β showed the opposite effects. Finally, urea production in cells was measured, and ammonia detoxification improved significantly in cells after transfection with HNF3β. HNF3β plays a vital role in regulation of CPS1 gene and could promote the metabolism of ammonia by regulating CPS1 expression.
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