Functional Analysis of the Sulfotransferase, SULT2B1

硫酸盐结合(磺化)是类固醇激素生物转化的重要途径。这些反应是由胞浆磺基转移酶(Sult)超家族催化的。在人类中，SULT2B1基因编码两种亚型，SULT2B1a和SULT2B1b，它们催化包括脱氢表雄酮和双氢睾酮在内的类固醇激素的磺化。SULT2B1在类固醇激素反应的组织中表达，包括前列腺和乳房。这项研究计划的目标是阐明一种由SULT2B1催化的新的调控途径，它可以废除类固醇激素依赖的细胞过程。拟议的研究将评估表达SULT2B1和自然产生的多态SULT2B1同工酶的细胞对雄激素的增殖和转录反应。在补充工作中，将评估SULT2B1中通过进化获得的新的富含脯氨酸的结构域对蛋白质-蛋白质相互作用的贡献的功能意义。最后，我们将评估常见基因SULT2B1多态的功能意义。总之，这些研究有可能阐明一种由SULT2B1催化的新的调控途径，它可以废除人类中依赖类固醇激素的细胞过程。

Sulfate conjugation (sulfonation) is an important pathway in the biotransformation of steroid hormones. These reactions are catalyzed by a superfamily of cytosolic sulfotransferase (SULT) enzymes. In humans, the SULT2B1 gene encodes two isoforms, SULT2B1a and SULT2B1b, that catalyze the sulfonation of steroid hormones including dehydroepiepiandrosterone and dihydrotestosterone. SULT2B1 is expressed in steroid hormone-responsive tissues including prostate and breast. The goal of this research proposal seeks to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid- hormone dependent cellular processes. The proposed studies will evaluate the proliferative and transcriptional responses of cells expressing SULT2B1 and naturally occurring polymorphic SULT2B1 alloenzymes toward androgens. In complementary work, the functional significance of an evolutionarily acquired, novel proline-rich domain in SULT2B1 will be evaluated for its contribution to protein-protein interactions. Finally, the functional significance of common genetic SULT2B1 polymorphisms will be evaluated. Together these studies have the potential to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid hormone-dependent cellular processes in humans.