Session: SUN 338-365-Metabolic & Stress Receptors in Energy Homeostasis
Poster Board SUN-348
In the Nuclear Receptor DNA Binding Project we use protein binding microarrays (PBMs) to comprehensively define the DNA binding specificity of NRs (http://nrdbs.ucr.edu). Here we present PBM data on wild type human TRα1, TRβ1 and TRβ2 binding 1000’s of unique DNA sequences in the presence and absence of their heterodimeric partner retinoid X receptor (RXRα) and triiodothyronine (T3). We compare the binding specificity of different TR mutants found in human HCC [hcI-TRα1 (K74E,A264V), hcM-TRα1 (K74R,M150T,E159K)], human RCCC [rc6-TRα1 (I116N,A225T,M388I), rc15-TRβ1 (K155E,K411E)] and oncogenic gag-v-Erb-A. Finally, we identify affinity altering single nucleotide polymorphisms (aaSNPs) in TR binding sites for TRα1, TRβ1 and TRβ2 heterodimers. These results will help characterize potential TR target genes in normal and cancerous cells, elucidate the mechanism by which TR mutants contribute to cancer and potentially identify populations susceptible to TR action. Our results could also potentially have implications for therapeutics.
Nothing to Disclose: NVT, JD, BF, MLP, FMS
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