ArticlePloS one2017
The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- 20(S)-Ginsenoside Rg3 Partially Induces Maturation of HepG2 Cells via the AMPK/HNF4A Pathway.Iranian journal of public health · 2025Article
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Early tolerance and late persistence as alternative drug responses in cancer.Nature communications · 2025Article
- Dengue virus NS1 leads to downregulation of HNF4 alpha in liver cells resulting in a decrease in coagulation factors I, V, X, and XIII, contributing to coagulopathy.Journal of virology · 2024Article
- Probenecid Inhibits Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Mitogen-Activated Protein Kinase Pathways in Regulating Respiratory Syncytial Virus Response.International journal of molecular sciences · 2024Article
- Molecular alterations associated with pathophysiology in liver-specific ZO-1 and ZO-2 knockout mice.Cell structure and function · 2024Article
- A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.EMBO molecular medicine · 2024Article
- Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction.Clinical and molecular hepatology · 2024Article
- Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.Brain, behavior, and immunity · 2024Article
- HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.Nature communications · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- Article
- Article
- Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators.Life (Basel, Switzerland) · 2023Review
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Article
- The transcription factor HNF-4α: a key player in haematological disorders.Archives of medical science : AMS · 2023Article
- Article
- The Expression Level of ABCC6 Transporter in Colon Cancer Cells Correlates with the Activation of Different Intracellular Signaling Pathways.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte nuclear factor 4 alpha (HNF4α) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4α is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4α. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4α. However, based on our previous results we hypothesized that HNF4α is also regulated at the post-transcriptional level by ERK1/2. Here we show that ERK1/2 is capable of directly phosphorylating HNF4α in vitro at several phosphorylation sites including residues previously shown to be targeted by other kinases, as well. Furthermore, we also demonstrate that phosphorylation of HNF4α leads to a reduced trans-activational capacity of the nuclear receptor in luciferase reporter gene assay. We confirm the functional relevance of these findings by demonstrating with ChIP-qPCR experiments that 30-minute activation of ERK1/2 leads to reduced chromatin binding of HNF4α. Accordingly, we have observed decreasing but not disappearing binding of HNF4α to the target genes. In addition, 24-hour activation of the pathway further decreased HNF4α chromatin binding to specific loci in ChIP-qPCR experiments, which confirms the previous reports on the decreased expression of the HNF4a gene due to ERK1/2 activation. Our data suggest that the ERK1/2 pathway plays an important role in the regulation of HNF4α-dependent hepatic gene expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.