Transcription of the Human Sodium Channel SCN1A Gene Is Repressed by a Scaffolding Protein RACK1

摘要: Voltage-gated sodium channel α subunit type I (Nav1.1, encoded by SCN1A gene) plays a critical role in the initiation of action potential central nervous system. Downregulated expression is believed to be associated with epilepsy. Here, we found that promoter (P1c), located at 5′ untranslated exon 1c, drove reporter gene human NT2 cells, and region between nt +53 +62 downstream P1c repressed activity. Further analyses showed scaffolding protein RACK1 (receptor for activated C kinase 1) was involved binding this silencer. Knockdown cells deprived repressive silencer on increased transcription, suggesting involvement negatively regulating transcription via interaction Furthermore, demonstrated complex including motif decreased neuron-like differentiation induced retinoic acid resulted upregulation transcription. Taken together, study reports novel participates acid-induced neuronal cells.