ArticleThe Biochemical journal2006
Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- TIFAB modulates metabolic pathways in KMT2A::MLLT3-induced AML through HNF4A.Blood advances · 2025Article
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Telomere Dysfunction Activates p53 and Represses HNF4α Expression Leading to Impaired Human Hepatocyte Development and Function.Hepatology (Baltimore, Md.) · 2020Article
- Review
- Interaction with p53 explains a pro-proliferative function for VHL in cancer.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4α and contributes to cell cycle control in hepatoma cells.Oncotarget · 2016Article
- Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.Molecular and cellular biology · 2015Article
- Regulation of hepatocyte identity and quiescence.Cellular and molecular life sciences : CMLS · 2015Review
- Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.Oncotarget · 2015Article
- The anti-hypercholesterolemic effect of low p53 expression protects vascular endothelial function in mice.PloS one · 2014Article
- HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR-122.PloS one · 2014Article
- The transcription factor p53: not a repressor, solely an activator.Cell cycle (Georgetown, Tex.) · 2014Article
- Article
- Localization of hepatocyte nuclear factor-4α in the nucleolus and nucleus is regulated by its C-terminus.Journal of diabetes investigation · 2012Article
- The yin and yang of proliferation and differentiation: cyclin D1 inhibits differentiation factors ChREBP and HNF4α.Cell cycle (Georgetown, Tex.) · 2012Article
- Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition.Biochemical and biophysical research communications · 2012Article
- p53 acts as a co-repressor to regulate keratin 14 expression during epidermal cell differentiation.PloS one · 2012Article
- Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation.Molecular and cellular biology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously shown that p53 inhibits the transactivation function of HNF (hepatocyte nuclear factor) 4alpha1, a nuclear receptor known to be critical for early development and liver differentiation. In the present study we demonstrate that p53 also down-regulates expression of the human HNF4alpha gene via the proximal P1 promoter. Overexpression of wild-type p53 down-regulated endogenous levels of both HNF4alpha protein and mRNA in Hep3B cells. This decrease was also observed when HepG2 cells were exposed to UV irradiation or doxorubicin, both of which increased endogenous p53 protein levels. Ectopically expressed p53, but not a mutant p53 defective in DNA binding (R249S), down-regulated HNF4alpha P1 promoter activity. Chromatin immunoprecipitation also showed that endogenous p53 bound the HNF4alpha P1 promoter in vivo after doxorubicin treatment. The mechanism by which p53 down-regulates the P1 promoter appears to be multifaceted. The down-regulation was partially recovered by inhibition of HDAC activity and appears to involve the positive regulator HNF6alpha. p53 bound HNF6alpha in vivo and in vitro and prevented HNF6alpha from binding DNA in vitro. p53 also repressed stimulation of the P1 promoter by HNF6alpha in vivo. However, since the R249S p53 mutant also bound HNF6alpha, binding HNF6alpha is apparently not sufficient for the repression. Implications of the p53-mediated repression of HNF4alpha expression in response to cellular stress are discussed.
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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.