p53-Independent Activation of the gadd45 Promoter by Δ12-Prostaglandin J2
| Autor: | Naoko Ohtani-Fujita, Sachiyo Mimaki, Shinji Minami, Toshiyuki Sakai, Su Dao |
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| Rok vydání: | 1998 |
| Předmět: |
Transcription
Genetic DNA repair DNA damage Recombinant Fusion Proteins Biophysics Transfection Biochemistry HeLa Transcription (biology) Prostaglandins Synthetic Humans RNA Messenger Cloning Molecular Promoter Regions Genetic Molecular Biology Gene biology Prostaglandin D2 Cell growth Intracellular Signaling Peptides and Proteins Proteins Promoter Cell Biology biology.organism_classification Molecular biology Kinetics Gene Expression Regulation Protein Biosynthesis Tumor Suppressor Protein p53 Cell Division DNA Damage HeLa Cells |
| Zdroj: | Biochemical and Biophysical Research Communications. 251:648-652 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1998.9511 |
| Popis: | A p53-inducible gene, the growth arrest and DNA damage-inducible gene 45 (gadd45), is associated with cell growth inhibition, DNA damage response and DNA repair. Here we report that Delta12-prostaglandin J2 (Delta12-PGJ2), an in vivo metabolite of arachidonic acid, which inhibits cell proliferation, induces gadd45 mRNA in HeLa cells. Because the p53 protein in HeLa cells is inactivated by papilloma virus E6, this type of gadd45 induction appears to be p53-independent. The induction was dose-dependent, and the maximum induction was observed at a concentration of 7.5 microgram/ml. In a time course study, gadd45 mRNA was induced 3 h after the addition of 7.5 microgram/ml Delta12-PGJ2. To investigate the transcriptional mechanism of gadd45 mRNA induction, we cloned a human genomic DNA fragment containing the gadd45 promoter region, and investigated the effect of Delta12-PGJ2 on the gadd45 promoter activity. In HeLa cells, 7.5 microgram/ml Delta12-PGJ2 markedly stimulated the gadd45 gene promoter about 20-fold or more. On the other hand, Delta12-PGJ2 did not stimulate the promoter activity of a reporter plasmid containing only p53 binding sites in HeLa cells, indicating that the gadd45 promoter activation by Delta12-PGJ2 was not mediated by p53. These results suggest that one of the mechanisms of cell growth arrest by Delta12-PGJ2 is mediated through a p53-independent induction of gadd45. |
| Databáze: | OpenAIRE |
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