ArticleMolecular and cellular biology2000
The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 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
96 citing papers in PubMed, 315 citations in OpenAlex.
- 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
- Gypensapogenin A-Liposomes Efficiently Ameliorates Hepatocellular Lipid Accumulation via Activation of FXR Receptor.Molecules (Basel, Switzerland) · 2024Article
- Gut microbiota depletion aggravates bile acid-induced liver pathology in mice with a human-like bile acid composition.Clinical science (London, England : 1979) · 2023Article
- Deletion of hepatic small heterodimer partner ameliorates development of nonalcoholic steatohepatitis in mice.Journal of lipid research · 2023Article
- HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.Frontiers in endocrinology · 2023Article
- Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Discovery of farnesoid X receptor and its role in bile acid metabolism.Molecular and cellular endocrinology · 2022Review
- Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease.Molecular metabolism · 2021Review
- The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Article
- Research on the circadian clock gene HNF4a in different malignant tumors.International journal of medical sciences · 2021Article
- Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation.Nature reviews. Endocrinology · 2020Review
- Overview of organic anion transporters and organic anion transporter polypeptides and their roles in the liver.World journal of clinical cases · 2019Review
- The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis.Biology of sex differences · 2019Review
- Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.Journal of lipid research · 2019Article
- Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma.Nature communications · 2018Article
- Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis.Endocrinology · 2018Article
- ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion.Nutrients · 2018Article
- Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR.Molecular metabolism · 2018Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The orphan nuclear hormone receptor SHP interacts with a number of other nuclear hormone receptors and inhibits their transcriptional activity. Several mechanisms have been suggested to account for this inhibition. Here we show that SHP inhibits transactivation by the orphan receptor hepatocyte nuclear factor 4 (HNF-4) and the retinoid X receptor (RXR) by at least two mechanisms. SHP interacts with the same HNF-4 surface recognized by transcriptional coactivators and competes with them for binding in vivo. The minimal SHP sequences previously found to be required for interaction with other receptors are sufficient for interaction with HNF-4, although deletion results indicate that additional C-terminal sequences are necessary for full binding and coactivator competition. These additional sequences include those associated with direct transcriptional repressor activity of SHP. SHP also competes with coactivators for binding to ligand-activated RXR, and based on the ligand-dependent interaction with other nuclear receptors, it is likely that coactivator competition is a general feature of SHP-mediated repression. The minimal receptor interaction domain of SHP is sufficient for full interaction with RXR, as previously described. This domain is also sufficient for full coactivator competition. Functionally, however, full inhibition of RXR transactivation requires the presence of the C-terminal repressor domain, with only weak inhibition associated with this receptor interaction domain. Overall, these results suggest that SHP represses nuclear hormone receptor-mediated transactivation via two separate steps: first by competition with coactivators and then by direct effects of its transcriptional repressor function.
Indexed as
Identifiers
What Socratic 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 Socratic graph.