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孤儿受体COUP-TF I拮抗视黄酸诱导的神经元分化。

Orphan receptor COUP-TF I antagonizes retinoic acid-induced neuronal differentiation.

作者信息

Neuman K, Soosaar A, Nornes H O, Neuman T

机构信息

Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.

出版信息

J Neurosci Res. 1995 May 1;41(1):39-48. doi: 10.1002/jnr.490410106.

DOI:10.1002/jnr.490410106
PMID:7674376
Abstract

Chicken ovalbumin upstream promoter-transcription factors (COUP-TF) are expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP-TF orphan receptors in neurogenesis is virtually unknown. To study the possible function of COUP-TF I during neuronal differentiation, we generated COUP-TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)-induced neuronal differentiation of these cells. COUP-TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP-TF I represses expression of microtubule-associated protein 2 (MAP2) gene and delays induction of growth-associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF-L) gene is not affected by COUP-TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP-TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP-TF I plays an important role in regulating RA-induced neuronal differentiation.

摘要

鸡卵清蛋白上游启动子转录因子(COUP-TF)在发育中的神经系统中表达,并与核激素受体相互作用以调节不同基因的表达。COUP-TF孤儿受体在神经发生中的作用几乎未知。为了研究COUP-TF I在神经元分化过程中的可能功能,我们构建了过表达COUP-TF I的畸胎瘤PCC7细胞系,并分析了这些细胞的视黄酸(RA)诱导的神经元分化。COUP-TF I的过表达导致诱导分化后形态分化的阻滞。COUP-TF I抑制微管相关蛋白2(MAP2)基因的表达,并延迟生长相关蛋白43(GAP43)基因表达的诱导。相反,在神经元分化过程中,神经丝轻链亚基(NF-L)基因的表达不受COUP-TF I过表达的影响。此外,过表达COUP-TF I的细胞在RA和二丁酰环磷腺苷(dBcAMP)处理后不会停止增殖,并且来自不同RA反应元件的转录激活受到抑制。这些结果表明,COUP-TF I在调节RA诱导的神经元分化中起重要作用。

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