Cyclophilin A (CyPA, also known as PPIA) is an abundant and ubiquitously expressed protein belonging to the immunophilin family, which has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymatic activity. CyPA mediates immunosuppressive action of the cyclic undecapeptide cyclosporine A and is also involved in multiple cellular processes, such as protein folding, intracellular trafficking, signal transduction and transcriptional regulation. CyPA is abundantly expressed in cancer cells, and, owing to its chaperone nature, its expression is induced upon the onset of stress. In this study, we demonstrated that a significant pool of this immunophilin is primarily an intramitochondrial factor that migrates to the nucleus when cells are stimulated with stressors. CyPA shows anti-apoptotic action per se and the capability of forming ternary complexes with cytochrome c and the small acidic co-chaperone p23, the latter interaction being independent of the usual association of p23 with the heat-shock protein of 90 kDa, Hsp90. These CyPA•p23 complexes enhance the anti-apoptotic response of the cell, suggesting that both proteins form a functional unit, the high level of expression of which plays a significant role in cell survival.

亲环素A（CyPA，也称为PPIA）是一种丰富且普遍表达的蛋白质，属于亲免素家族，具有内在的肽基-脯氨酰-（顺/反)-异构酶酶活性。CyPA 介导环状十一肽环孢菌素 A 的免疫抑制作用，并且还参与多种细胞过程，例如蛋白质折叠、细胞内运输、信号转导和转录调节。CyPA 在癌细胞中大量表达，并且由于其伴侣性质，它的表达在应激开始时被诱导。在这项研究中，我们证明了这种免疫亲和素的重要池主要是线粒体内因子，当细胞受到压力源刺激时，它会迁移到细胞核。CyPA 本身显示出抗凋亡作用以及与细胞色素 c 和小的酸性辅助伴侣 p23 形成三元复合物的能力，后者的相互作用独立于 p23 与 90 kDa 的热休克蛋白 Hsp90 的通常结合。