Quinotrierixin inhibited ER stress-induced XBPl mRNA splicing through inhibition of protein synthesis

Abstract

Quinotrierixin was isolated from microbes as an inhibitor of ER stress-induced XBPl mRNA splicing, but its mode of action was unclear. We found that quinotrierixin is an inhibitor of protein synthesis, and that the required dose range of quinotrierixin to inhibit ER stress-induced XBPl mRNA splicing was similar to that to inhibit protein synthesis. Furthermore, we also found that quinotrierixin inhibited the ER stress-induced increases of unfolded protein response-related genes such as GRP78, CHOP, EDEM, ERdj4, and p58IPK. Thus, we showed that quinotrierixin inhibited the ER stress-induced unfolded protein response, possibly due to its inhibitory activity of protein synthesis.