亲环素A表达和定位改变对p19胚胎癌细胞分化的影响。 - Suppr | 超能文献

亲环素A表达和定位改变对p19胚胎癌细胞分化的影响。

Effects of altered expression and localization of cyclophilin A on differentiation of p19 embryonic carcinoma cells.

Chiu Robert, Rey Osvaldo, Zheng Jun-Qi, Twiss Jeffery L, Song Jun, Pang Shen, Yokoyama Kazunari K

Dental Research Institute, UCLA School of Dentistry, Los Angeles, California 90095-1668, USA.

Cell Mol Neurobiol. 2003 Dec;23(6):929-43. doi: 10.1023/b:cemn.0000005321.11544.cc.

Abstract

The retinoblastoma susceptibility gene product, p105Rb (RB), is an important regulator in the control of cell proliferation, differentiation, and apoptosis. Several cellular factors that complex with RB and exert their cellular regulatory functions have been identified, such as the RB:cyclophilin A (CypA) complex. 2. CypA is a cytoplasmic immunophilin and known for its involvement in T-cell differentiation and proliferation. Although CypA has a pivotal role in the immune response, its function in other signaling pathways is largely unknown. 3. In this study, we used a model of neuronal differentiation to demonstrate that the nuclear translocation of CypA, the appearance of hypophosphorylated RB and the enhancement of RB: CypA complex formation correlates with retinoic acid induced neuronal differentiation. 4. Inhibition of CypA expression results in repression of both the hypophosphorylated RB and the neuron-specific differentiation marker, class III beta tubulin. 5. The evidence of enriched CypA and colocalization of RB with CypA in the nucleus of primary adult sensory neurons substantiated the important event of RB-mediated neuronal differentiation of p19 EC cells.

摘要

视网膜母细胞瘤易感基因产物p105Rb（RB）是细胞增殖、分化及凋亡调控中的重要调节因子。已鉴定出几种与RB结合并发挥细胞调节功能的细胞因子，如RB：亲环素A（CypA）复合物。2. CypA是一种细胞质亲环蛋白，以参与T细胞分化和增殖而闻名。尽管CypA在免疫反应中起关键作用，但其在其他信号通路中的功能大多未知。3. 在本研究中，我们使用神经元分化模型来证明，CypA的核转位、低磷酸化RB的出现以及RB：CypA复合物形成的增强与视黄酸诱导的神经元分化相关。4. 抑制CypA表达会导致低磷酸化RB和神经元特异性分化标志物Ⅲ型β微管蛋白均受到抑制。5. 在原代成年感觉神经元细胞核中CypA富集以及RB与CypA共定位的证据证实了RB介导的p19 EC细胞神经元分化这一重要事件。