Choline kinase alpha expression during RA-induced neuronal differentiation: Role of C/EBPβ
Choline kinase alpha expression during RA-induced neuronal differentiation: Role of C/EBPβ
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DOI：
10.1016/j.bbalip.2014.01.007
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Banchio, Claudia
中科院分区：
文献类型：
--
作者：
Domizi, Pablo;Aoyama, Chieko;Banchio, Claudia
神经元分化是一个复杂的过程，其特征在于停止增殖和神经突从细胞体延伸。这个过程伴随着基因表达的变化，介导导致神经突形成和功能的重定向。膜磷脂合成的加速与神经突伸长相关，并且磷脂酰胆碱（PtdCho）是哺乳动物细胞中的主要膜磷脂。特别是编码用于PtdCho生物合成的CDP-胆碱途径中的关键酶的两个基因的转录被刺激; Chka基因用于胆碱激酶（CK）α同种型，Pcyt 1a基因用于CTP：磷酸胆碱胞苷酰转移酶（CCT）α同种型。我们报告，在视黄酸（RA）诱导分化过程中，CK α表达的刺激依赖于一个启动子区域，该区域包含两个CCAAT/增强子结合蛋白-β（C/EBP β）位点。我们证明，在神经元分化的神经元-2a细胞，RA诱导Chka表达的机制，涉及ERK 1/2激活触发C/EBP β表达。升高水平的C/EBP β与Chka近端启动子（Box 1）结合，诱导CK α表达。此外，我们鉴定了命名为Box 2的下游序列，其与Box 1一起是启动子达到完全诱导所需的。这是第一次阐明的机制，其中表达的Chka协调调节神经元分化。(C)2014爱思唯尔有限公司版权所有。
Neuronal differentiation is a complex process characterized by a halt in proliferation and extension of neurites from the cell body. This process is accompanied by changes in gene expression that mediate the redirection leading to neurite formation and function. Acceleration of membrane phospholipids synthesis is associated with neurite elongation, and phosphatidylcholine (PtdCho) is the major membrane phospholipid in mammalian cells. The transcription of two genes in particular encoding key enzymes in the CDP-choline pathway for PtdCho biosynthesis are stimulated; the Chka gene for choline kinase (CK) alpha isoform and the Pcyt1a gene for the CTP: phosphocholine cytidylyltransferase (CCT) alpha isoform. We report that the stimulation of CK alpha expression during retinoic acid (RA) induced differentiation depends on a promoter region that contains two CCAAT/Enhancer-binding Protein-beta (C/EBP beta) sites. We demonstrate that during neuronal differentiation of Neuro-2a cells, RA induces Chka expression by a mechanism that involves ERK1/2 activation which triggers C/EBP beta expression. Elevated levels of C/EBP beta bind to the Chka proximal promoter (Box1) inducing CK alpha expression. In addition we identified a downstream sequence named Box2 which together with Box1 is required for the promoter to reach the full induction. This is the first elucidation of the mechanism by which the expression of Chka is coordinately regulated during neuronal differentiation. (C) 2014 Elsevier B.V. All rights reserved.