Cyclophilin A Is Required for Retinoic Acid-induced Neuronal Differentiation in p19 Cells*
Cyclophilin A Is Required for Retinoic Acid-induced Neuronal Differentiation in p19 Cells*
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DOI：
10.1074/jbc.m311406200
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发表时间：
2004-06
影响因子：
4.8
通讯作者：
Jun Song;Yingchun Lu;K. Yokoyama;J. Rossi;R. Chiu
中科院分区：
文献类型：
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作者：
Jun Song;Yingchun Lu;K. Yokoyama;J. Rossi;R. Chiu
在p19细胞中表达针对亲环素A(CypA)的小干扰RNA的稳定转基因细胞失去了其在维甲酸(RA)诱导的神经元分化方面的潜力，但不能诱导Me2SO诱导的中胚层分化。这一差异表明CypA是RA诱导的神经通路所特需的。除了RA诱导的RA受体β表达和视黄酸反应元件(REARE)结合活性的丧失外，在CypA基因敲除细胞系中，RA诱导的REARE介导的荧光素酶活性显著降低，这表明CypA影响REARE介导的基因表达调节。靶序列的沉默突变证实了RNA干扰在p19胚胎癌细胞中的特异性。总之，我们的数据表明，CypA在RA诱导的p19胚胎癌细胞神经分化过程中需要一个新的功能。
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 Me2SO-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 β 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.