ArticleMolecular and cellular biology1997
Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- A genetic variation associated with plasma erythropoietin and a non-coding transcript of PRKAR1A in sickle cell disease.Human molecular genetics · 2016Pooled it
- Silencing lipid catabolism determines longevity in response to fasting.Nature communications · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Hnf4α integrates AIF and caspase 3/9 signaling to restrict single and coinfecting pathogens in teleosts.PLoS pathogens · 2025Article
- A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.EMBO molecular medicine · 2024Article
- Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.The Journal of clinical investigation · 2023Article
- Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.Gastro hep advances · 2023Article
- The transcription factor HNF-4α: a key player in haematological disorders.Archives of medical science : AMS · 2023Article
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia.Nature communications · 2022Article
- Role of the macula densa sodium glucose cotransporter type 1-neuronal nitric oxide synthase-tubuloglomerular feedback pathway in diabetic hyperfiltration.Kidney international · 2022Article
- Regulation of Liver Regeneration by Hepatocyte O-GlcNAcylation in Mice.Cellular and molecular gastroenterology and hepatology · 2022Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- Multiomics Analyses of HNF4α Protein Domain Function during Human Pluripotent Stem Cell Differentiation.iScience · 2019Article
- Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia.Journal of the American Society of Nephrology : JASN · 2019Article
- Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor.Stem cell reports · 2017Article
- Hypoxia reduces HNF4α/MODY1 protein expression in pancreatic β-cells by activating AMP-activated protein kinase.The Journal of biological chemistry · 2017Article
- The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2.PloS one · 2017Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Transcriptional and Chromatin Regulation during Fasting - The Genomic Era.Trends in endocrinology and metabolism: TEM · 2015Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte nuclear factor 4 (HNF4), a liver-enriched transcription factor of the nuclear receptor superfamily, is critical for development and liver-specific gene expression. Here, we demonstrate that its DNA-binding activity is modulated posttranslationally by phosphorylation in vivo, ex vivo, and in vitro. In vivo, HNF4 DNA-binding activity is reduced by fasting and by inducers of intracellular cyclic AMP (cAMP) accumulation. A consensus protein kinase A (PKA) phosphorylation site located within the A box of its DNA-binding domain has been identified, and its role in phosphorylation-dependent inhibition of HNF4 DNA-binding activity has been investigated. Mutants of HNF4 in which two potentially phosphorylatable serines have been replaced by either neutral or charged amino acids were able to bind DNA in vitro with affinity similar to that of the wild-type protein. However, phosphorylation by PKA strongly repressed the binding affinity of the wild-type factor but not that of HNF4 mutants. Accordingly, in transfection assays, expression vectors for the mutated HNF4 proteins activated transcription more efficiently than that for the wild-type protein-when cotransfected with the PKA catalytic subunit expression vector. Therefore, HNF4 is a direct target of PKA which might be involved in the transcriptional inhibition of liver genes by cAMP inducers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.