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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...

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Related Experiment Video

Updated: Jun 4, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Using nuclear receptor activity to stratify hepatocarcinogens.

Imran Shah1, Keith Houck, Richard S Judson

  • 1National Center for Computational Toxicology, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America. shah.imran@epa.gov

Plos One
|February 23, 2011
PubMed
Summary

Environmental chemicals activating human nuclear receptors (NR) were analyzed for rodent liver cancer links. Potent NR activators in vitro were linked to rodent carcinogens, suggesting NR activity predicts toxicity.

Related Experiment Videos

Last Updated: Jun 4, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Area of Science:

  • Environmental toxicology
  • Molecular toxicology
  • Nuclear receptor signaling

Background:

  • Nuclear receptors (NR) are critical transcription factors regulating cellular functions.
  • Persistent NR stimulation can cause non-genotoxic rodent liver cancer, with uncertain human relevance.
  • This study investigates 309 environmental chemicals for human NR activity and rodent liver cancer outcomes.

Purpose of the Study:

  • To systematically analyze in vitro human NR activity data for 309 environmental chemicals.
  • To correlate human NR activity patterns with chronic liver cancer-related outcomes in rodents.
  • To assess the utility of in vitro assays for stratifying environmental contaminants.

Main Methods:

  • In vitro assays determined the effects of 309 chemicals on human constitutive androstane receptors (CAR), pregnane X receptor (PXR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptors (PPAR), liver X receptors (LXR), retinoic X receptors (RXR), and steroid receptors (SR).
  • Rodent liver histopathology from chronic studies was graded for cancer lesion progression.
  • Multivariate analysis was used to identify NR activity patterns and their association with rodent liver cancer severity.

Main Results:

  • Chemicals causing proliferative liver lesions in both rats and mice showed significantly higher activity for human PPAR, PXR, and CAR compared to those affecting only one species.
  • Most chemicals displayed promiscuous NR activation, clustering into distinct activity patterns.
  • Human NR activity patterns of chemicals were weakly associated with the severity of rodent liver cancer progression.

Conclusions:

  • Rodent carcinogens exhibited higher in vitro potency for human NR than non-carcinogens.
  • Similar NR promiscuity patterns across diverse chemicals showed weak associations with rodent liver cancer severity.
  • In vitro NR activity assays can help stratify environmental contaminants based on human bioactivity and rodent toxicity, offering insights into potential toxicity pathways.