title: CRELD2 is a novel endoplasmic reticulum stress-inducible gene.
abstract: Recently, endoplasmic reticulum (ER) stress responses have been suggested to play important roles in maintaining various cellular functions and to underlie many tissue dysfunctions. In this study, we first identified cysteine-rich with EGF-like domains 2 (CRELD2) as an ER stress-inducible gene by analyzing a microarray analysis of thapsigargin (Tg)-inducible genes in Neuro2a cells. CRELD2 mRNA is also shown to be immediately induced by treatment with the ER stress-inducing reagents tunicamycin and brefeldin A. In the genomic sequence of the mouse CRELD2 promoter, we found a typical ER stress responsible element (ERSE), which is well conserved among various species. Using a luciferase reporter analyses, we demonstrated that the ERSE in mouse CRELD2 is functional and responds to Tg and ATF6-overexpression. Each mutation of ATF6- or NF-Y-binding sites in the ERSE of the mouse CRELD2 promoter dramatically decreased both the basal activity and responsiveness toward the ER stress stimuli. Our study suggests that CRELD2 could be a novel mediator in regulating the onset and progression of various ER stress-associated diseases.
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu, Japan. oohashi@gifu-u.ac.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oh-hashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Koga
authors.forename: Shun
authors.initials: S
authors.lastname: Ikeda
authors.forename: Kiyo
authors.initials: K
authors.lastname: Shimada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirata
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Kiuchi
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D051702:Activating Transcription Factor 6; D006023:Glycoproteins