Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Sci Signal. 2011 Mar 15;4(164):rs2. doi: 10.1126/scisignal.2001449.
Chemically induced proximity (CIP) systems use small molecules and engineered proteins to control and study biological processes. However, small molecule-based systems for controlling protein abundance or activities have been limited by toxicity, instability, cost, and slow clearance of the small molecules in vivo. To address these problems, we modified proteins of the plant abscisic acid (ABA) stress response pathway to control the proximity of cellular proteins and showed that the system could be used to regulate transcription, signal transduction, and subcellular localization of proteins in response to exogenously applied ABA. We also showed that the ABA CIP system can be combined with other CIP systems to simultaneously control multiple processes. We found that, when given to mice, ABA was orally available and had a 4-hour half-life. These properties, along with its lack of toxicity and low cost, suggest that ABA may be well suited for therapeutic applications and as an experimental tool to control diverse cellular activities in vivo.
化学诱导邻近（CIP）系统使用小分子和工程蛋白来控制和研究生物过程。然而，基于小分子的控制蛋白质丰度或活性的系统受到毒性、不稳定性、成本和小分子在体内清除缓慢的限制。为了解决这些问题，我们修改了植物脱落酸（ABA）应激反应途径的蛋白质，以控制细胞蛋白质的邻近，并表明该系统可用于调节转录、信号转导和蛋白质的亚细胞定位，以响应外源施加的 ABA。我们还表明，ABA CIP 系统可以与其他 CIP 系统结合使用，以同时控制多个过程。我们发现，当给予小鼠时，ABA 可口服且半衰期为 4 小时。这些特性，以及其无毒和低成本，表明 ABA 可能非常适合治疗应用，并作为一种实验工具，用于控制体内多种细胞活动。
