The Border Biomedical Research Center and Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
Curr Opin Pharmacol. 2011 Aug;11(4):314-9. doi: 10.1016/j.coph.2011.03.010. Epub 2011 Apr 19.
The large FK506-binding protein FKBP52 has been characterized as an important positive regulator of androgen, glucocorticoid and progesterone receptor signaling pathways. FKBP52 associates with receptor-Hsp90 complexes and is proposed to have roles in both receptor hormone binding and receptor subcellular localization. Data from biochemical and cellular studies have been corroborated in whole animal models as fkbp52-deficient male and female mice display characteristics of androgen, glucocorticoid and/or progesterone insensitivity. FKBP52 receptor specificity and the specific phenotypes displayed by the fkbp52-deficient mice have firmly established FKBP52 as a promising target for the treatment of a variety of hormone-dependent diseases. Recent studies demonstrated that the FKBP52 FK1 domain and the proline-rich loop within this domain are functionally important for FKBP52 regulation of receptor function. Based on these data, efforts are currently underway to target the FKBP52 FK1 domain and the proline-rich loop with small molecule inhibitors.
大型 FK506 结合蛋白 FKBP52 已被确定为雄激素、糖皮质激素和孕激素受体信号通路的重要正调控因子。FKBP52 与受体-Hsp90 复合物结合，并被认为在受体激素结合和受体亚细胞定位中具有作用。来自生化和细胞研究的数据在整体动物模型中得到了证实，因为 FKBP52 缺陷的雄性和雌性小鼠表现出雄激素、糖皮质激素和/或孕激素不敏感的特征。FKBP52 受体特异性和 FKBP52 缺陷小鼠表现出的特定表型，使 FKBP52 成为治疗各种激素依赖性疾病的有前途的靶点。最近的研究表明，FKBP52 的 FK1 结构域和该结构域内的富含脯氨酸环对于 FKBP52 调节受体功能是功能上重要的。基于这些数据，目前正在努力用小分子抑制剂靶向 FKBP52 的 FK1 结构域和富含脯氨酸环。
