Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Regulation of BiP gene expression by cyclopentenone prostaglandins through unfolded protein response element. 866 2

Cyclopentenone prostaglandins (PGs), such as 15-deoxy-12,13-didehydro-14,15-didehydro-PGJ2 (15d-delta(12,14)-PDJ2), 12,13-didehydro-PGJ2 (delta12-PGJ2) and PGA2, are actively transported into cells and promote the expression of a variety of genes. The ultimate metabolite of PGD2, 15d-delta(12,14)-PGJ2, specifically binds to a nuclear receptor, the gamma isoform of the peroxisome proliferator-activated receptor, thereby promoting adipogenesis. Cyclopentenone PGs also induce the expression of various stress genes, such as heat shock proteins (HSPs), the immunoglobulin heavy chain binding protein (BiP) and protein disulfide isomerase by acting through heat shock element or unfolded protein response element. Overall, cyclopentenone PGs regulate cell growth, cell differentiation and stress responses by regulating various gene expression.
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PMID:Cyclopentenone prostaglandin receptors. 1243 47