Basic research for development of new type of drugs based on the mechanism of transcriptional regulation

转录调控是通过各种特异性相互作用的组合进行的，例如DNA-蛋白质和蛋白质-蛋白质相互作用。由于转录是调控基因表达的主要反应，其调控机制的破坏可能导致疾病。这一领域的研究被认为是新药开发的适当目标。本研究主要包括以下几个方面：1）新型转录因子的筛选为了筛选出参与DNA-蛋白质和蛋白质-蛋白质相互作用的转录调控辅助因子，本研究采用双杂交筛选系统，以已知的转录因子为探针，筛选出新的转录调控辅助因子。因此，已经分离出各种因子，包括参与自身免疫性疾病的肉瘤基因产物和核因子的候选因子。2）药物筛选系统的构建由于双杂交筛选系统可以检测转录因子之间的相互作用，因此该系统也被认为适用于分离对相互作用具有抑制活性的药物。用于药物开发的其他筛选系统正在开发中，利用转录活性和DNA与转录因子之间的相互作用的测定。

Transcriptional regulation is carried out by the combination of various specific interactions such as DNA-protein and protein-protein interactions. Since transcription is the main reaction in regulating gene expression, the destruction of its regulatory mechanism may cause diseases. The research of this area is regarded as an appropriate target for new drug development. Our research includes the following.1) Isolation of new type of transcription factors for drug developmentIn order to isolate new co-factors participating in DNA-protein and protein-protein interactions in transcriptional regulation, the two-hybrid screening system has been applied with the known factors as the probe. As a result, various factors have been isolated including candidate factors for sarcoma gene products and nuclear factors participating in autoimmune diseases. This methodology has been shown to be effective in the isolation of target factors for developing drugs.2) Construction of a system for screening in drug developmentAs interactions between transcription factors can be detected by using two-hybrid screening system, the system is also thought to be adequate for the isolation of drugs which show inhibition activities on interactions. Other screening systems for drug development are under development, utilizing assays of transcriptional activity and the interactions between DNA and transcription factors.