基于蛋白质相互作用网络的PXR调控研究进展

Research updates on PXR regulation based on protein-protein interaction

环境应答基因孕烷受体(pregnane X receptor,NR1I2,PXR/SXR)是目前肝脏代谢中最重要的核受体之一,在内外源物质代谢稳态进程中,同时发挥着感受器和效应器的关键作用,广泛参与葡萄糖代谢,肿瘤耐药,以及炎症反应。迄今为止,PXR作为转录因子调控细胞色素P450酶系已经有很充分的研究,但是PXR的相互作用蛋白质网络为它参与蛋白质的表观遗传修饰,调控生命活动提供了新的可能。本文综述了在表观遗传修饰领域一些能够与PXR发生反应的重要蛋白质-蛋白质相互作用,如PXR与甲基化转移酶、乙酰化转移酶以及泛素、类泛素连接酶之间的相互作用,有助于开展PXR在细胞应激反应领域新功能的探索,对于进一步阐明环境应答基因参与调控生命学事件将具有重要意义。

Environmental responsive gene pregnane X receptor(PXR)is one of the most important nuclear receptors that acts as both a"sensor"and an"effector"regulating glucose metabolism,drug resistance,and inflammation.So far,it is well-established that PXR transcriptionally regulate the expression of some CYP450 enzymes;however,PXR-mediated protein-protein interaction unraveled PXR’s novel functions beyond transcriptional regulation.In this article,we reviewed some interactions that occurred between PXR and critical proteins in epigenetic modifications,such as the interactions of PXR with methyltransferases,acetyltransferases,and ubiquitin and SUMO(small ubiquitin-related modifier)ligases,which may help us better understand the role of PXR in cellular stress and clarify the mechanisms of environmental responsive genes regulating biotic events.