Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system - Evidence for a role in neurite outgrowth
Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system - Evidence for a role in neurite outgrowth
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DOI：
10.1074/jbc.274.33.23128
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发表时间：
1999-08-13
影响因子：
4.8
通讯作者：
Puymirat, J
中科院分区：
文献类型：
--
作者：
Denver, RJ;Ouellet, L;Puymirat, J
甲状腺激素(3，5，3‘-三碘甲状腺原氨酸；T-3)对脊椎动物大脑的正常发育是必不可少的，影响神经元迁移、髓鞘形成、轴突成熟和树突状突起生长等多种过程。我们已经鉴定出碱性转录元件结合蛋白(BTEB)是一种小的GC盒结合蛋白，在发育中的大鼠脑中是一个受T-3调节的基因。大脑皮层BTEB基因的表达具有发育调节和甲状腺激素依赖性。T-3对BTEB mRNA的调节是神经细胞特异性的，在胚胎神经元(E16)和新生星形胶质细胞(P2)的原代培养中上调，但在新生少突胶质细胞(P2)中不上调。T-3在表达甲状腺激素受体(TR)p1的神经2a细胞中迅速上调BTEB mRNA，但在表达trα1的细胞中不上调，表明该基因的调节是trβ1亚型特有的，一些证据支持T-3对BTEB基因表达的转录作用。BTEB在Neuro-2a细胞中的过表达以剂量依赖的方式显着增加了神经突起的数量和长度，表明该转录因子在神经元突起的形成中发挥了作用。然而，其他依赖T-3的改变没有改变，即BTEB的过表达对细胞的增殖率和乙酰胆碱酯酶活性的表达没有影响。
Thyroid hormone (3,5,3'-triiodothyronine; T-3) is essential for normal development of the vertebrate brain, influencing diverse processes such as neuronal migration, myelin formation, axonal maturation, and dendritic outgrowth. We have identified basic transcription element-binding protein (BTEB), a small GC box-binding protein, as a T-3-regulated gene in developing rat brain. BTEB mRNA levels in cerebral cortex exhibit developmental regulation and thyroid hormone dependence. T-3 regulation of BTEB mRNA is neural cell specific, being up-regulated in primary cultures of embryonic neurons (E16) and in neonatal astrocytes (P2), but not in neonatal oligodendrocytes (P2), T-3 rapidly up-regulated BTEB mRNA in neuro-2a cells engineered to express thyroid hormone receptor (TR) pi but not in cells expressing TR alpha 1, suggesting that the regulation of this gene is specific to the TR beta 1 isoform, Several lines of evidence support a transcriptional action of T-3 on BTEB gene expression. Overexpression of BTEB in Neuro-2a cells dramatically increased the number and length of neurites in a dose-dependent manner suggesting a role for this transcription factor in neuronal process formation. However, other T-3-dependent changes were not altered; i.e. overexpression of BTEB had no effect on the rate of cell proliferation nor on the expression of acetylcholinesterase activity.