Evidence map›Paper›PMID 21292004›Full record

ArticlePharmacological research2011

NCOA6 differentially regulates the expression of the CYP2C9 and CYP3A4 genes.

Sailesh Surapureddi, Ritu Rana, Joyce A Goldstein

Open access · greenAbstract read
In one paragraph

Article in Pharmacological research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 16% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study.Toxicology in vitro : an international journal published in association with BIBRA · 2019
    Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Sailesh SurapureddiLaboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, United States.
Ritu Rana
Joyce A Goldstein
National Institute of Environmental Health Sciences · US

Funding

Drug Metabolizing Enzymes In Humans And Animal ModelsZIAES021024 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GOLDSTEIN, JOYCE · 2009 to 2015
$11.0M
Intramural NIH HHS ZIA ES021024NIEHS NIH HHS Z01ES02124
6 · The paper itself

Abstract

CYP2Cs and CYP3A4 sub families of enzymes of the Cytochrome P450 super family metabolize clinically prescribed therapeutics. Constitutive and induced expressions of these enzymes are under the control of HNF4α and rifampicin activated PXR. In the present study, we show a mechanism for ligand dependent synergistic cross talk between PXR and HNF4α. Two-hybrid screening identified NCOA6 as a HNF4α interacting protein. NCOA6 was also found to interact with PXR through the first LXXLL motif in GST pull down and mammalian two hybrid assays. NCOA6 enhances the synergistic activation of CYP2C9 and CYP3A4 promoter activity by PXR and HNF4α in the presence of rifampicin. However silencing NCOA6 abrogated the synergistic activation and induction of CYP2C9 by PXR-HNF4α but not of CYP3A4. ChIP analysis revealed that NCOA6 could bridge HNF4α and PXR binding sites of the CYP2C9 promoter. Our results indicate that NCOA6 is responsible for the synergistic activation of CYP2C9 by HNF4α and PXR and NCOA6 differentially regulates CYP2C9 and CYP3A4 gene expression though both the genes are regulated by the same nuclear receptors.

Indexed as

Gene Expression Regulation, EnzymologicAryl Hydrocarbon HydroxylasesChromatin ImmunoprecipitationCytochrome P-450 CYP2C9Cytochrome P-450 CYP3AHepatocyte Nuclear Factor 4Hep G2 CellsHumansNuclear Receptor CoactivatorsPregnane X ReceptorProtein Interaction MappingReceptors, SteroidTwo-Hybrid System TechniquesAryl Hydrocarbon HydroxylasesCYP2C9 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP2C9Cytochrome P-450 CYP3AHepatocyte Nuclear Factor 4NCOA6 protein, humanNuclear Receptor CoactivatorsPregnane X ReceptorReceptors, Steroid

Identifiers

PMID21292004
PMCPMC3082001
OpenAlexW2056345858

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.