Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
J Neuroendocrinol. 2018 Feb;30(2). doi: 10.1111/jne.12484.
Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) is an oestrogen receptor (ER) coregulator protein identified by our collaborative group. Work from our laboratory and others has shown that PELP1 is a scaffold protein that interacts with ERs and kinase signalling factors, as well as proteins involved in chromatin remodelling and DNA repair. Its role in mediating 17β-oestradiol (E ) signalling and actions has been studied in detail in cancer cells, although only recently has attention turned to its role in the brain. In this review, we discuss the tissue, cellular and subcellular localisation of PELP1 in the brain. We also discuss recent evidence from PELP1 forebrain-specific knockout mice demonstrating a critical role of PELP1 in mediating both extranuclear and nuclear ER signalling in the brain, as well as E -induced neuroprotection, anti-inflammatory effects and regulation of cognitive function. Finally, the PELP1 interactome and unique gene network regulated by PELP1 in the brain is discussed, especially because it provides new insights into PELP1 biology, protein interactions and mechanisms of action in the brain. As a whole, the findings discussed in the present review indicate that PELP1 functions as a critical ER coregulator in the brain to mediate E signalling and actions.
脯氨酸、谷氨酸和亮氨酸丰富蛋白 1（PELP1）是由我们的合作小组发现的雌激素受体（ER）辅助调节蛋白。本实验室和其他实验室的工作表明，PELP1 是一种支架蛋白，可与 ER 和激酶信号因子相互作用，以及与染色质重塑和 DNA 修复相关的蛋白质。虽然最近才开始关注其在大脑中的作用，但它在介导 17β-雌二醇（E ）信号和作用方面在癌细胞中的作用已得到详细研究。在这篇综述中，我们讨论了 PELP1 在大脑中的组织、细胞和亚细胞定位。我们还讨论了最近来自 PELP1 前脑特异性敲除小鼠的证据，这些证据表明 PELP1 在介导大脑中的核外和核 ER 信号以及 E 诱导的神经保护、抗炎作用和认知功能调节中起着关键作用。最后，讨论了 PELP1 在大脑中的相互作用组和受 PELP1 调控的独特基因网络，特别是因为它为 PELP1 在大脑中的生物学、蛋白质相互作用和作用机制提供了新的见解。总的来说，本综述中讨论的发现表明，PELP1 作为 ER 在内脑的关键辅助调节因子，介导 E 信号和作用。
