TR4 ORPHAN RECEPTOR IN TESTIS

描述：睾丸孤儿受体4(TR4)最初是从 P.I.的前列腺和睾丸基因文库(Chang et al，1994)。初步 研究表明，TR4可能属于雌激素受体/甲状腺。 受体核受体亚家族与AGGTCA直接结合 重复着。功能分析表明，TR4对维甲酸有抑制作用 (RA)诱导的反式激活，识别HIV-I和SV40中的DNA启动子，以及 诱导CNTFR基因表达。TR4还可以调节甲状腺。 激素、维生素D和PPARpha信号级联，并发挥负性活动 促红细胞生成素基因的表达。我们的初步数据发现， RXR、PPARpha和CNTFR也可以控制TR4的表达， 在TR4和其他设备之间提供双向反馈和控制机制 信号通路。 基于上述数据，调查人员提出了以下5个目标 进一步鉴定前列腺和睾丸中的TR4。 目的1)分离可调节细胞周期的辅因子(辅活化子/辅抑制子) TR4功能。 目的2)5‘端启动子的鉴定和顺式作用元件的分离 控制TR4的表达。 目的3)分离控制基因表达的反式作用因子(TAFs TR4. 目的4)鉴定TR4的配体或激活剂。 目的5)研究睾丸组织中P53和TR4的相互作用。 这项提案的成功完成可能有助于我们更好地理解 TR4的分子机制及其潜在的生化功能。

DESCRIPTION: The testicular orphan receptor 4 (TR4) was initially cloned from prostate and testes cDNA libraries by the P.I.(Chang et al, 1994). Preliminary studies indicated that the TR4 might belong to the estrogen receptor/thyroid receptor nuclear receptor subfamily due to its ability to bind to AGGTCA direct repeats. Functional analysis showed that the TR4 could suppress retinoic acid (RA)-induced transactivation, recognize a DNA promoter in HIV-I and SV40, and induce the CNTFR gene expression. The TR4 can also modulate the thyroid hormone, Vitamin D, and PPARalpha signal cascades, and exert negative activity on erythropoietin gene expression. Our preliminary data found that ligands for RXR, PPARalpha, and CNTFR could also control the expression of the TR4, providing a bi-directional feedback, control mechanism between TR4 and other signaling pathways. Based on the above data, the investigators propose the following 5 aims to further characterize the TR4 in the prostate and testis. Aim 1) Isolation of cofactors (coactivators/corepressors) that can modulate the TR4 functions. Aim 2) 5' promoter characterization and isolation of cis-acting elements that control expression of the TR4. Aim 3) Isolation of trans-acting factors (TAFs) that control expression of the TR4. Aim 4) Identification of ligands or activators for TR4. Aim 5) Study cross talk between p53 and TR4 in testes. The successful completion of this proposal may help us to better understand the molecular mechanism of the TR4 and its potential biochemical functions.