論文 - 詳細
| RRC ID | 45786 |
|---|---|
| 著者 | Leung CK, Hasegawa K, Wang Y, Deonarine A, Tang L, Miwa J, Choe KP. |
| タイトル | Direct interaction between the WD40 repeat protein WDR-23 and SKN-1/Nrf inhibits binding to target DNA. |
| ジャーナル | Mol Cell Biol |
| Abstract |
SKN-1/Nrf transcription factors activate cytoprotective genes in response to reactive small molecules and strongly influence stress resistance, longevity, and development. The molecular mechanisms of SKN-1/Nrf regulation are poorly defined. We previously identified the WD40 repeat protein WDR-23 as a repressor of Caenorhabditis elegans SKN-1 that functions with a ubiquitin ligase to presumably target the factor for degradation. However, SKN-1 activity and nuclear accumulation are not always correlated, suggesting that there could be additional regulatory mechanisms. Here, we integrate forward genetics and biochemistry to gain insights into how WDR-23 interacts with and regulates SKN-1. We provide evidence that WDR-23 preferentially regulates one of three SKN-1 variants through a direct interaction that is required for normal stress resistance and development. Homology modeling predicts that WDR-23 folds into a β-propeller, and we identify the top of this structure and four motifs at the termini of SKN-1c as essential for the interaction. Two of these SKN-1 motifs are highly conserved in human Nrf1 and Nrf2 and two directly interact with target DNA. Lastly, we demonstrate that WDR-23 can block the ability of SKN-1c to interact with DNA sequences of target promoters identifying a new mechanism of regulation that is independent of the ubiquitin proteasome system, which can become occupied with damaged proteins during stress. |
| 巻・号 | 34(16) |
| ページ | 3156-67 |
| 公開日 | 2014-8-1 |
| DOI | 10.1128/MCB.00114-14 |
| PII | MCB.00114-14 |
| PMID | 24912676 |
| PMC | PMC4135592 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA, Protozoan / genetics DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Gene Expression Regulation / genetics Larva / metabolism Longevity / genetics Protein Binding Protein Folding Repressor Proteins / genetics Repressor Proteins / metabolism* Stress, Physiological / genetics Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 3.611 |
| 引用数 | 10 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1817 |