ArticleThe Journal of biological chemistry2010
The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors.Cancer cell international · 2025Review
- Molecular mechanism of specific DNA sequence recognition by NRF1.Nucleic acids research · 2024Article
- Biology and therapeutic applications of the proton-coupled folate transporter.Expert opinion on drug metabolism & toxicology · 2022Article
- The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance.Cancer cell international · 2021Article
- Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds.British journal of cancer · 2020Article
- Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1.The Biochemical journal · 2019Article
- High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Nuclear Respiratory Factor 1 Negatively Regulates the P1 Promoter of the Peroxisome Proliferator-Activated Receptor-γ Gene and Inhibits Chicken Adipogenesis.Frontiers in physiology · 2018Article
- Nuclear Respiratory Factor 1 (NRF-1) Controls the Activity Dependent Transcription of the GABA-A Receptor Beta 1 Subunit Gene in Neurons.Frontiers in molecular neuroscience · 2018Article
- Regulation of Reduced Folate Carrier (RFC) by Vitamin D Receptor at the Blood-Brain Barrier.Molecular pharmaceutics · 2017Article
- Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons.Scientific reports · 2017Article
- The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption.Molecular aspects of medicine · 2017Review
- Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC.Scientific reports · 2016Article
- Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription.Science advances · 2016Article
- Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect.Journal of clinical biochemistry and nutrition · 2014Article
- Vitamin D is not linked to folate status and mRNA expression of intestinal proton-coupled folate transporter.European journal of nutrition · 2014Article
- The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Enhanced receptor-mediated endocytosis and cytotoxicity of a folic acid-desacetylvinblastine monohydrazide conjugate in a pemetrexed-resistant cell line lacking folate-specific facilitative carriers but with increased folate receptor expression.Molecular pharmacology · 2014Article
- Selective accumulation of hematoporphyrin derivative in glioma through proton-coupled folate transporter SLC46A1.Journal of clinical biochemistry and nutrition · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Folates are essential vitamins that play a key role as one-carbon donors in a spectrum of biosynthetic pathways including RNA and DNA synthesis. The proton-coupled folate transporter (PCFT/SLC46A1) mediates obligatory intestinal folate absorption. Loss-of-function mutations in PCFT result in hereditary folate malabsorption, an autosomal recessive disorder characterized by very low folate levels in the blood and cerebrospinal fluid. Hereditary folate malabsorption manifests within the first months after birth with anemia, immune deficiency, and neurological deficits. Here we studied the role of inducible trans-activators of PCFT gene expression. Bioinformatics identified three putative nuclear respiratory factor 1 (NRF-1) binding sites in the minimal promoter. The following evidence establish that PCFT is an NRF-1-responsive gene; electrophoretic mobility shift assay showed NRF-1 binding to native but not mutant NRF-1 sites, whereas antibody-mediated supershift analysis and chromatin immunoprecipitation revealed NRF-1 binding to its consensus sites within the PCFT promoter. Moreover, mutational inactivation of individual or all NRF-1 binding sites resulted in 40-60% decrease in luciferase reporter activity. Consistently, overexpression of NRF-1 or a constitutively active NRF-1 VP-16 construct resulted in increased reporter activity and PCFT mRNA levels. Conversely, introduction of a dominant-negative NRF-1 construct markedly repressed reporter activity and PCFT mRNA levels; likewise, introduction of NRF-1 siRNA duplexes to cells resulted in decreased PCFT transcript levels. Moreover, NRF-1 silencing down-regulated genes encoding for key folate transporters and enzymes in folate metabolism. These novel findings identify NRF-1 as a major inducible transcriptional regulator of PCFT gene expression. The implications of this linkage between folate transport and metabolism with mitochondria biogenesis and respiration are discussed.
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