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

Cyclopentenone prostaglandins (PGs) are transported into cells and stimulate the expression of various stress genes, such as that coding for BiP (an ER luminal protein). To reveal the site of action of the PGs for the induction of stress-gene expression, we introduced a fluorescent probe, pyrene, into two types of PG analogue, GIF0010 (a cyclopentenone type) and GIF0037 (a cyclopentanone type) and examined their intracellular localization in normal rat kidney cells and their ability to induce the BiP gene expression. GIF0010 accumulated around the nuclei and coincided with BiP, a resident protein in the endoplasmic reticulum (ER) and markedly induced BiP gene expression. By contrast, GIF0037 and pyrene neither accumulated in the cell nor induced BiP gene expression. Thus the ER localization of GIF0010 and the induction of gene expression by GIF0010 are ascribed to the cyclopentenone structure. Treatment with cycloheximide inhibited both the accumulation of GIF0010 and the induction of the BiP mRNA, suggesting that the ER localization of the PG and subsequent gene expression require the nascent protein synthesis. These results demonstrate that the cyclopentenone PG is specifically accumulated in the ER, transducing a signal for BiP gene expression in the nuclei.
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PMID:Localization of a cyclopentenone prostaglandin to the endoplasmic reticulum and induction of BiP mRNA. 974 10

Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G(1) phase in vitro and to suppress tumor growth in vivo. However, their effects on neurons are unclear. Here, we report that some cyclopentenone PGs function as neurite outgrowth-promoting factors. They promoted neurite outgrowth from PC12 cells and from dorsal root ganglion explants but only in the presence of nerve growth factor (NGF). We refer to these PGs as neurite outgrowth-promoting PGs (NEPPs). Through study of the structure-function relationship of NEPP1-10 and related compounds, we found that the cross-conjugated dienone moiety of NEPPs was essential for promoting neurite outgrowth, and NEPP10 was concluded to be the best candidate for drug development. We also investigated the intracellular mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin heavy chain binding protein/glucose-regulated protein 78 (BiP/GRP78) plays a role in the promotion, based on the following observations: Antisense nucleotides for BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein level increased in response to NEPPs; and overexpression of BiP/GRP78 protein by adenoviral gene transfer promoted the neurite outgrowth by NGF.
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PMID:Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor. 1093 91

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