Departments of Urology, and Biochemistry and Molecular Biology, New York University School of Medicine, New York, NY, USA.
Institute for Systems Genetics, New York University School of Medicine, New York, NY, USA.
Adv Exp Med Biol. 2018;1106:85-94. doi: 10.1007/978-3-030-00737-9_6.
The Unconventional prefoldin RPB5 interacting protein (URI), also known as RPB5-Mediating Protein (RMP) has been shown to play several regulatory roles in different cellular compartments including the mitochondria, as a phosphatase binding protein; in the cytoplasm, as a chaperone-like protein; and in the nucleus, as a transcriptional regulator through binding to RPB5 and RNA polymerase II (polII). This chapter focuses on the role URI plays in transcriptional regulation in the prostate cell. In prostate cells, URI is tightly bound to another prefoldin-like protein called UXT, a known androgen receptor (AR) cofactor. Part of a multiprotein complex, URI and UXT act as transcriptional repressors, and URI regulates KAP1 through PP2A phosphatase activity. The discovery of the interaction of URI and UXT with KAP1, AR, and PP2A, as well as the numerous interactions between URI and components of the R2TP/prefoldin-like complex, RPB5, and nuclear proteins involved in DNA damage response, chromatin remodeling and gene transcription, reveal a pleiotropic effect of the URI/UXT complex on nuclear processes. The mechanisms by which URI/UXT affect transcription, chromatin structure and regulation, and genome stability, remain to be elucidated but will be of fundamental importance considering the many processes affected by alterations of URI/UXT and other prefoldins and prefoldin-like proteins.
非传统的前折叠体 RPB5 相互作用蛋白（URI），也称为 RPB5 介导蛋白（RMP），已被证明在不同的细胞区室中发挥多种调节作用，包括线粒体，作为磷酸酶结合蛋白；在细胞质中，作为伴侣样蛋白；在细胞核中，作为转录调节剂，通过与 RPB5 和 RNA 聚合酶 II（polII）结合。本章重点介绍 URI 在前列腺细胞中的转录调节作用。在前列腺细胞中，URI 与另一种称为 UXT 的前折叠体样蛋白紧密结合，UXT 是一种已知的雄激素受体（AR）共因子。作为多蛋白复合物的一部分，URI 和 UXT 作为转录抑制剂，URI 通过 PP2A 磷酸酶活性调节 KAP1。URI 和 UXT 与 KAP1、AR 和 PP2A 的相互作用的发现，以及 URI 与 R2TP/前折叠体样复合物、RPB5 和参与 DNA 损伤反应、染色质重塑和基因转录的核蛋白的众多相互作用，揭示了 URI/UXT 复合物对核过程的多效性影响。URI/UXT 影响转录、染色质结构和调节以及基因组稳定性的机制仍有待阐明，但考虑到 URI/UXT 和其他前折叠体和前折叠体样蛋白的改变影响到许多过程，这些机制将具有重要的基础性意义。
