Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Sydney Medical School Nepean, Faculty of Medicine and Health, The University of Sydney, Nepean Hospital, Penrith, NSW 2750, Australia.
Int J Mol Sci. 2022 Jul 25;23(15):8174. doi: 10.3390/ijms23158174.
The P2X7 receptor (P2X7R) is an ATP-gated membrane ion channel that is expressed by multiple cell types. Following activation by extracellular ATP, the P2X7R mediates a broad range of cellular responses including cytokine and chemokine release, cell survival and differentiation, the activation of transcription factors, and apoptosis. The P2X7R is made up of three P2X7 subunits that contain specific domains essential for the receptor's varied functions. Alternative splicing produces P2X7 isoforms that exclude one or more of these domains and assemble in combinations that alter P2X7R function. The modification of the structure and function of the P2X7R may adversely affect cellular responses to carcinogens and pathogens, and alternatively spliced (AS) P2X7 isoforms have been associated with several cancers. This review summarizes recent advances in understanding the structure and function of AS P2X7 isoforms and their associations with cancer and potential role in modulating the inflammatory response.
P2X7 受体（P2X7R）是一种由多种细胞类型表达的 ATP 门控膜离子通道。在细胞外 ATP 激活后，P2X7R 介导广泛的细胞反应，包括细胞因子和趋化因子的释放、细胞存活和分化、转录因子的激活以及细胞凋亡。P2X7R 由三个 P2X7 亚基组成，这些亚基包含对受体多种功能至关重要的特定结构域。选择性剪接产生的 P2X7 异构体排除了一个或多个这些结构域，并以改变 P2X7R 功能的组合方式组装。P2X7R 的结构和功能的改变可能会对细胞对致癌剂和病原体的反应产生不利影响，并且剪接变体（AS）P2X7 异构体与几种癌症有关。本综述总结了对 AS P2X7 异构体的结构和功能及其与癌症的关联以及在调节炎症反应中的潜在作用的最新认识进展。
