Identification of Molecular Targets for Valproic Acid in Membrane Transport System Using Fission Yeast Model Organism

丙戊酸（VPA）被广泛用作抗惊厥药。最近有报道称，VPA增强了抗癌药物的作用，提高了多能干细胞诱导过程中的重编程效率，并显著促进了神经干细胞移植后后肢功能的恢复。VPA在这些情况下的确切作用机制尚不清楚，尽管它已被证明可以改变多种信号通路。为了进一步了解药物作用的分子机制，我们开发了一种基因筛选，用于裂变酵母中对VPA过敏的突变体。我们发现VPA参与细胞膜内运输。

Valproic acid (VPA) is widely used as an anticonvulsant. More recently, it has been reported that VPA reinforces action of the anticancer drug, improves the reprogramming efficiency in the induction of pluripotent stem cells, and dramatically enhances the restoration of hind limb function after transplantation of neural stem cells. The exact mechanisms of action of VPA in these conditions remain unclear, although it has been shown to alter a wide variety of signaling pathways. To gain further insights into the molecular mechanisms of drug action, we have developed a genetic screen for mutants that show hypersensitivity to VPA in fission yeast. We found that VPA is involved in intracellular membrane trafficking.