Hawley R J, Scheibe R J, Wagner J A
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
J Neurosci. 1992 Jul;12(7):2573-81. doi: 10.1523/JNEUROSCI.12-07-02573.1992.
NGF is a peptide growth factor that plays a key role in the differentiation and survival of neurons in both the PNS and CNS. NGF acts through both transcription-dependent and transcription-independent mechanisms to regulate the differentiation of PC12 cells. To better understand the regulation of gene expression by NGF, we have defined a cis-acting sequence that is immediately upstream of the transcription start site of the VGF (a2/NGF33.1) gene that is required for induction by NGF. Within this sequence is a consensus cAMP response element (CRE) embedded in a 14 base pair palindrome. Mutations in this CRE eliminate induction of the VGF gene both by NGF and by agents that act via cAMP. Although this sequence confers transcriptional induction by both NGF and cAMP, it is not sufficient to allow induction by epidermal growth factor, acidic or basic fibroblast growth factor, or phorbol 12-myristate 13-acetate (PMA). Thus, this sequence defines an element that is selectively activated by NGF and cAMP. Promoter fragments from the VGF gene that include the core CRE efficiently bind the inducible transcription factor CREB, while fragments bearing mutations that eliminate NGF and cAMP inducibility fail to do so. Sequence comparisons and hybridization studies indicate that there are at least two alternatively spliced forms of VGF mRNA, and the accumulation of both of these forms is similarly regulated by NGF and cAMP.
神经生长因子（NGF）是一种肽类生长因子，在周围神经系统（PNS）和中枢神经系统（CNS）的神经元分化和存活中起关键作用。NGF通过转录依赖性和转录非依赖性机制调节PC12细胞的分化。为了更好地理解NGF对基因表达的调控，我们确定了一个顺式作用序列，它位于VGF（a2/NGF33.1）基因转录起始位点的紧邻上游，是NGF诱导所必需的。在这个序列中有一个嵌入14个碱基对回文结构中的共有cAMP反应元件（CRE）。这个CRE中的突变消除了NGF和通过cAMP起作用的试剂对VGF基因的诱导。尽管这个序列赋予了NGF和cAMP转录诱导作用，但它不足以允许表皮生长因子、酸性或碱性成纤维细胞生长因子或佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）进行诱导。因此，这个序列定义了一个被NGF和cAMP选择性激活的元件。来自VGF基因的包含核心CRE的启动子片段能有效结合可诱导转录因子CREB，而带有消除NGF和cAMP诱导性突变的片段则不能。序列比较和杂交研究表明，VGF mRNA至少有两种可变剪接形式，并且这两种形式的积累都受到NGF和cAMP的类似调控。
