Song Jun, Lu Ying-Chun, Yokoyama Kazunari, Rossi John, Chiu Robert
Dental Research Institute, UCLA School of Dentistry, Los Angeles, California 90095, USA.
J Biol Chem. 2004 Jun 4;279(23):24414-9. doi: 10.1074/jbc.M311406200. Epub 2004 Mar 26.
Stable transfectants with expression of small interfering RNA for targeting cyclophilin A (CypA) in p19 cells lose their potential for retinoic acid (RA)-induced neuronal differentiation but not Me(2)SO-induced mesodermal differentiation. This difference suggests that CypA is specifically required for the RA-induced neuronal pathway. In addition to the loss of RA-induced RA receptor beta expression and retinoic acid response element (RARE)-binding activity, a dramatic reduction in RA-induced RARE-mediated luciferase activity in the CypA knockdown cell line suggests that CypA affects RARE-mediated regulation of gene expression. Silent mutation of target sequences confirms the specificity of RNA interference in p19 embryonal carcinoma cells. Collectively, our data reveal that a novel function of CypA is required in the processing of RA-induced neuronal differentiation in p19 embryonal carcinoma cells.
在p19细胞中稳定转染靶向亲环素A（CypA）的小干扰RNA后，细胞失去了视黄酸（RA）诱导的神经元分化潜能，但未失去二甲基亚砜（Me2SO）诱导的中胚层分化潜能。这种差异表明，CypA是RA诱导的神经元分化途径所特需的。除了RA诱导的视黄酸受体β表达及视黄酸反应元件（RARE）结合活性丧失外，在CypA敲低细胞系中，RA诱导的RARE介导的荧光素酶活性显著降低，这表明CypA影响RARE介导的基因表达调控。靶序列的沉默突变证实了p19胚胎癌细胞中RNA干扰的特异性。总体而言，我们的数据揭示了CypA在p19胚胎癌细胞RA诱导的神经元分化过程中具有一种新功能。
