論文 - 詳細
| RRC ID | 42356 |
|---|---|
| 著者 | Ishikawa M, Numazawa S, Yoshida T. |
| タイトル | Redox regulation of the transcriptional repressor Bach1. |
| ジャーナル | Free Radic Biol Med |
| Abstract |
Bach1 is a transcriptional repressor of heme oxygenase-1, one of the most inducible phase 2 proteins. Bach1 binds in conjunction with a small Maf protein to tandem repeats of the antioxidant response element (ARE) and quenches the target gene expression. On the other hand, the transactivator Nrf2 binds and up-regulates the ARE-governed gene expression. By using a sulfhydryl oxidizing agent, diamide, here we provide evidence which indicates that the Bach1 function is regulated by the redox state. Diamide showed restricted Nrf2 nuclear translocation and ARE-driven reporter activity but reversed the ARE transcriptional activity suppressed by ectopically expressed Bach1. Substitution of the conserved cysteine residue in the DNA binding domain of Bach1 to serine (C574S mutant) caused a refractory response to the diamide-mediated reactivation of the Bach1-suppressed reporter activity. Moreover, diamide induced cytoplasmic translocation of the GFP-Bach1 fusion protein but failed to translocate the fusion protein consisting of the C574S mutant. These data suggest that redox regulation of Bach1 is an alternative mechanism to induce multiple ARE-governed genes. |
| 巻・号 | 38(10) |
| ページ | 1344-52 |
| 公開日 | 2005-5-15 |
| DOI | 10.1016/j.freeradbiomed.2005.01.021 |
| PII | S0891-5849(05)00039-0 |
| PMID | 15855052 |
| MeSH | Animals Antioxidants / metabolism* Basic-Leucine Zipper Transcription Factors COS Cells Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology Cell Nucleus / metabolism Chlorocebus aethiops Cytoplasm / metabolism DNA-Binding Proteins / metabolism Diamide / pharmacology Fanconi Anemia Complementation Group Proteins Gene Expression Regulation* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Leucine Zippers Liver Neoplasms / metabolism Liver Neoplasms / pathology Mutagenesis, Site-Directed NF-E2-Related Factor 2 Oxidation-Reduction* Plasmids Promoter Regions, Genetic Protein Transport Recombinant Fusion Proteins / metabolism Repressor Proteins / metabolism* Response Elements / genetics* Trans-Activators / metabolism Transcription Factors / genetics* Transcription Factors / metabolism Transcription, Genetic* Transcriptional Activation |
| IF | 6.17 |
| 引用数 | 73 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 COS-7(RCB0539) |