Related Experiment Video
Updated: Aug 20, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Isolation and functional analysis of a keratinocyte-derived, ligand-regulated nuclear receptor comodulator
Anthony M Flores1, Lu Li, Brian J Aneskievich
1Graduate Program in Toxicology, School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA.
Abstract:
Keratinocyte (KC) gene expression is regulated by members of the nuclear receptor (NR) superfamily including retinoic acid receptors, retinoid X receptors (RAR and RXR, respectively), and peroxisome proliferator activated receptors (PPAR). In addition to ligand, NR transcriptional activity is controlled by interaction with proteins, collectively known as coregulators, which function as corepressors or coactivators. To improve our understanding of coregulators expressed in epidermis, we screened a KC cDNA library for PPARalpha-interacting proteins. The screen yielded previously unknown proteins including one we named COPR1, for comodulator of PPAR and RXR. COPR1 and its longer variant COPR2 target the AF-2 domains of NR but exhibit quantitative differences in their functional interactions with RAR, RXRalpha and PPAR. They decrease but do not completely repress the activity of RXRalpha and PPARalpha because of a proline-acid-rich autonomous activation domain. An NR box motif contributes to but is not solely responsible for functional and physical association with RXRalpha. The activation domain, their relatively small size (COPR1, 26.9 kDa; COPR2, 32.4 kDa), and strict dependence on AF-2 for interaction distinguish COPR1 and COPR2 from the SMRT/NCoR type of corepressor and may represent a means of control that dampens rather than completely represses NR-mediated gene expression.
Related Concept Videos
Regulation of Nuclear Protein Sorting
Signal Transduction: Overview
Typically, signal transduction involves three...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Co-activators and Co-repressors
Internal Receptors
Combinatorial Gene Control
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

