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K. Petrukhin, F. Fonseca, Q. Qin; Co-Regulator Role of NR2E3 in Mediation of Nuclear Receptor Signaling. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1672.
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Nuclear receptors (NR) comprise a family of transcription factors involved in regulation of a variety of biological processes. Nuclear receptor signaling involves ligand-dependent interaction with transcriptional co-regulators (co-repressors and co-activators). We previously established that NR2E3 may function as a classic nuclear receptor: it forms homodimers on several response elements, silences basal transcription in the absence of ligand, and interacts with corepressors NCOR, SMRT in the unliganded state. Here we describe a set of experiments establishing a new NR2E3 role as a unique photoreceptor-specific transcriptional coregulator modulating the function of other member of nuclear receptor superfamily
We used a mammalian two-hybrid system to demonstrate that NR2E3 interacts with other nuclear receptors when they have the agonist-induced conformation. Formation of NR-NR2E3 complexes has been confirmed in vitro using a time-resolved fluorescence energy transfer technique. Co-immunoprecipitation and electrophoretic mobility shift assays confirmed formation of the NR-NR2E3 complexes. We used mutagenesis scanning to map the protein regions responsible for NR-NR2E3 interaction
We demonstrated that NR2E3 forms complexes with a number of Type I and Type II nuclear receptors when they have the agonist-induced conformation that favor coactivator binding.
In addition to being a classic nuclear receptor, NR2E3 may act as a distinct photoreceptor-specific coregulator capable of attenuating signaling from agonist-bound nuclear receptors through direct competition with established transcriptional coactivators.
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