title: Transcriptional activation of ATF6 by endoplasmic reticulum stressors.
abstract: Previous studies have shown that modification of activating transcription factor 6 (ATF6) protein is important for the endoplasmic reticulum (ER) stress response; ER stressors stimulate the degradation of ATF6 by Site-1 protease (S1P) and Site-2 protease (S2P) into p50-ATF6, which acts as a transcription factor. In the current study, we found that all of the ER stressors tested (such as thapsigargin) up-regulate ATF6 mRNA expression. As thapsigargin did not affect the stability of the ATF6 mRNA, it was concluded that this up-regulation is due to transcriptional activation of ATF6. An inhibitor of S1P suppressed this up-regulation of ATF6 mRNA expression and putative ATF6-binding elements in the promoter of ATF6 were identified, suggesting that p50-ATF6 positively regulates the gene expression of ATF6. Since cells over-expressing ATF6 showed an enhanced ER stress response, we propose that up-regulation of ATF6 mRNA expression is involved in enhancing the ER stress response.
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Namba
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishihara
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hoshino
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D012333:RNA, Messenger