title: Quinotrierixin inhibited ER stress-induced XBP1 mRNA splicing through inhibition of protein synthesis.
abstract: Quinotrierixin was isolated from microbes as an inhibitor of ER stress-induced XBP1 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 XBP1 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 p58(IPK). Thus, we showed that quinotrierixin inhibited the ER stress-induced unfolded protein response, possibly due to its inhibitory activity of protein synthesis.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Etsu
authors.initials: E
authors.lastname: Tashiro
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D058767:Protein Unfolding / Q000187:drug effects; D012326:RNA Splicing / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C532275:quinotrierixin; D017828:Rifabutin; D000841:Anisomycin; D003513:Cycloheximide