Abstract
Delta12-Prostaglandin (PG) J2, a cyclopentenone prostaglandin, plays a role in various stress responses. BiP, a stress-inducible chaperone protein, is implicated in protein folding and translocation in endoplasmic reticulum and induced in the condition of accumulation of unfolded proteins. Here, we examined the effect of Delta12-PGJ2 on the expression of the BiP gene. Delta12-PGJ2 markedly stimulated the expression of the BiP gene in a time- and concentration-dependent manner in HeLa cells. This stimulation was specific for cyclopentenone PGs among various PGs. Cycloheximide pretreatment completely inhibited the Delta12-PGJ2-induced expression of the BiP gene, suggesting that the effects on nascent protein synthesis are involved in the signaling mechanism. Delta12-PGJ2 markedly stimulated the promoter activity of the 5'-flanking region of the BiP gene through the unfolded protein response element. Furthermore, Delta12-PGJ2 stimulated the enhancer activity of the 3'-half of the unfolded protein response element, and this stimulation required three nucleotides within this region. Gel mobility shift assay demonstrated that this region was occupied with two specific nuclear protein factors with different mobilities in the control cells, and Delta12-PGJ2 induced the dissociation of the protein-DNA complex with lower mobility. These findings indicate that Delta12-PGJ2 stimulates the expression of BiP gene through the 3'-half of the unfolded protein response element.
Highlights
Gel requirement of de novo protein synthesis for the cyclopentenone PG-induced gene expression suggests that the site of stress actions of the PGs may be on the regulation of nascent protein processing
Induction of BiP mRNA by ⌬12-PGJ2—We examined the effect of ⌬12-PGJ2 on the expression of the BiP gene in HeLa cells by Northern blot analysis
We examined the specificity of stimulation of the BiP gene expression for various PGs
Summary
⌬12-PGJ2 markedly stimulated the promoter activity of the 5-flanking region of the BiP gene through the unfolded protein response element. ⌬12PGJ2 stimulated the enhancer activity of the 3-half of the unfolded protein response element, and this stimulation required three nucleotides within this region. Gel requirement of de novo protein synthesis for the cyclopentenone PG-induced gene expression suggests that the site of stress actions of the PGs may be on the regulation of nascent protein processing.
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