Human TR2 and TR3 orphan receptors, identified in our laboratory, are proteins with unknown functions that share structural homology with the steroid receptor superfamily. They may bind with-yet unidentified ligands and play very important roles in the signal transduction or cell proliferation. Characterization of TR2/3 orphan receptors in this proposal may, therefore, help to expand our understanding of the diversity in structural and cellular responses that result from new hormonal action in cells and tissues. The long term goals of this project are to understand the biochemical/physiological properties of these two orphan receptors and their possible roles in the growth of prostate. We will attempt to identify and characterize genomic structures and loci of TIC orphan receptors in order to understand possible coding/noncoding domain resemblance. With this information, we can investigate the cis- and trans-acting regulatory elements within the 5 flanking sequences of their genes to elucidate the basal and Specific expression regulation (Specific Aim 3 & 4). These regulatory mechanisms might link with other signal transduction systems in the prostate. Furthermore, we will produce and purify TR213 orphan receptor proteins from baculovirus expression system (Specific Aim l) to initiate the study of target genes of TR2/3 orphan receptors (Specific Aim 2). From these studies, we may be able to identify some new hormone systems that may have valuable biological and physiological implication. For instance, TR3 orphan receptor may be the first member of steroid receptor superfamily that can be regulated by autocrine growth factors and androgens in the prostate. Therefore, it may be a good candidate to link these two signal transduction systems which play very important roles in the prostate. Our discovery that androgen can repress the TR2 orphan receptor mRNA in prostate may also put the TR2 orphan receptor as a potential new hormone system that may be related to later stage of prostate tumor growth when androgen can no longer control the prostate growth.
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