論文 - 詳細
| RRC ID | 51352 |
|---|---|
| 著者 | Wu CW, Wang Y, Choe KP. |
| タイトル | F-Box Protein XREP-4 Is a New Regulator of the Oxidative Stress Response in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
The transcription factor SKN-1 (Skinhead family member-1) in Caenorhabditis elegans is a homolog of the mammalian Nrf-2 protein and functions to promote oxidative stress resistance and longevity. SKN-1 mediates protection from reactive oxygen species (ROS) via the transcriptional activation of genes involved in antioxidant defense and phase II detoxification. Although many core regulators of SKN-1 have been identified, much remains unknown about this complex signaling pathway. We carried out an ethyl methanesulfonate (EMS) mutagenesis screen and isolated six independent mutants with attenuated SKN-1-dependent gene activation in response to acrylamide. All six were found to contain mutations in F46F11.6/xrep-4 (xenobiotics response pathways-4), which encodes an uncharacterized F-box protein. Loss of xrep-4 inhibits the skn-1-dependent expression of detoxification genes in response to prooxidants and decreases survival of oxidative stress, but does not shorten life span under standard culture conditions. XREP-4 interacts with the ubiquitin ligase component SKR-1 and the SKN-1 principal repressor WDR-23, and knockdown of xrep-4 increases nuclear localization of a WDR-23::GFP fusion protein. Furthermore, a missense mutation in the conserved XREP-4 F-box domain that reduces interaction with SKR-1 but not WDR-23 strongly attenuates SKN-1-dependent gene activation. These results are consistent with XREP-4 influencing the SKN-1 stress response by functioning as a bridge between WDR-23 and the ubiquitin ligase component SKR-1. |
| 巻・号 | 206(2) |
| ページ | 859-871 |
| 公開日 | 2017-6-1 |
| DOI | 10.1534/genetics.117.200592 |
| PII | genetics.117.200592 |
| PMID | 28341649 |
| PMC | PMC5499191 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* DNA-Binding Proteins / genetics* F-Box Proteins / genetics* Mutation, Missense Nuclear Proteins / genetics* Oxidative Stress / genetics* Repressor Proteins SKP Cullin F-Box Protein Ligases / genetics* Transcription Factors / genetics* |
| IF | 4.015 |
| 引用数 | 9 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 |