Oertle Thomas, Huber Chantal, van der Putten Herman, Schwab Martin E
Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology, Switzerland.
J Mol Biol. 2003 Jan 10;325(2):299-323. doi: 10.1016/s0022-2836(02)01179-8.
The reticulon-family member Nogo-A is a potent neurite growth inhibitory protein in vitro and may play a role in the restriction of axonal regeneration after injury and of structural plasticity in the CNS of higher vertebrates. Of the three major isoforms of Nogo, Nogo-A is mostly expressed in the brain, Nogo-B is found in a ubiquitous pattern, and Nogo-C is most highly expressed in muscle. Seven additional splice-variants derived both from differential splicing and differential promoter usage have been identified. Analysis of the TATA-less Nogo-A/B promoter (P1) shows that conserved GC-boxes and a CCAAT-box within the first 500bp upstream of the transcription start are responsible for its regulation. No major differences in the methylation status of the P1 CpG-island in tissues expressing or not expressing Nogo-A/B could be detected, suggesting that silencer elements are involved in the regulation. The specific expression pattern of Nogo-A/B is due to differential splicing. The basal Nogo-C promoter (P2) is regulated by a proximal and a distal element. The 5'UTR of Nogo-C harbours a negative control element. These data may help to identify factors that can modulate Nogo transcription, thus offering an alternative approach for Nogo neutralisation.
网织蛋白家族成员Nogo-A在体外是一种有效的神经突生长抑制蛋白，可能在高等脊椎动物中枢神经系统损伤后轴突再生的限制和结构可塑性中发挥作用。在Nogo的三种主要亚型中，Nogo-A主要在脑中表达，Nogo-B以普遍存在的模式分布，而Nogo-C在肌肉中表达最高。已经鉴定出另外七种由不同剪接和不同启动子使用产生的剪接变体。对无TATA框的Nogo-A/B启动子（P1）的分析表明，转录起始上游前500bp内保守的GC框和一个CCAAT框负责其调控。在表达或不表达Nogo-A/B的组织中，未检测到P1 CpG岛甲基化状态的主要差异，这表明沉默元件参与了调控。Nogo-A/B的特异性表达模式归因于不同的剪接。基础Nogo-C启动子（P2）受一个近端元件和一个远端元件调控。Nogo-C的5'非翻译区含有一个负调控元件。这些数据可能有助于识别能够调节Nogo转录的因子，从而为中和Nogo提供一种替代方法。
