Kim Soo-A, Choi Hong Seok, Ahn Sang-Gun
Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju, South Korea.
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Oncotarget. 2016 Dec 20;7(51):85381-85392. doi: 10.18632/oncotarget.13377.
PIN1, which belongs to a family of prolyl isomerases, specifically binds to phosphorylated Ser/Thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. This study aimed to investigate the importance of Pin1 expression in human dental pulp cells (hDPCs) to understand the involvement of Pin1 in the regulation of P2Y1 and the activation of ADP-mediated P2Y1 signaling. This study found that the protein levels of P2Y1 gradually decreased after the onset of cell recovery following heat stress. Interestedly, hDPC migration significantly decreased during the recovery period. An in vitro study revealed that the silencing of PIN1 by siRNA or the pharmacologic inhibition of its activity decreased the migration of P2Y1 and P2Y1 expression in these cells. In addition, we found that Pin1 directly interacts with S252 of P2Y1 and that its binding stabilizes the P2Y1 protein to increase migration activity. These results strongly suggest that Pin1 mediates cell migration by stabilizing P2Y1 and that the Pin1/P2Y1 signaling pathways might serve as a novel mechanism of cell migration progression in hDPCs.
PIN1属于脯氨酰异构酶家族，它特异性结合磷酸化的丝氨酸/苏氨酸-脯氨酸基序，以催化调节其底物的磷酸化后构象。本研究旨在探讨Pin1在人牙髓细胞（hDPCs）中表达的重要性，以了解Pin1在P2Y1调节及ADP介导的P2Y1信号激活中的作用。本研究发现，热应激后细胞恢复开始时，P2Y1的蛋白水平逐渐降低。有趣的是，hDPC迁移在恢复期显著减少。一项体外研究表明，通过siRNA沉默PIN1或对其活性进行药物抑制，会降低这些细胞中P2Y1的迁移和P2Y1表达。此外，我们发现Pin1直接与P2Y1的S252相互作用，其结合可稳定P2Y1蛋白以增加迁移活性。这些结果有力地表明，Pin1通过稳定P2Y1介导细胞迁移，且Pin1/P2Y1信号通路可能是hDPCs中细胞迁移进程的一种新机制。
