論文 - 詳細
| RRC ID | 59599 |
|---|---|
| 著者 | Spatola BN, Lo JY, Wang B, Curran SP. |
| タイトル | Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates. |
| ジャーナル | Sci Rep |
| Abstract |
Maintaining a healthy cellular environment requires the constant control of proteostasis. E3 ubiquitin ligase complexes facilitate the post-translational addition of ubiquitin, which based on the quantity and specific lysine linkages, results in different outcomes. Our studies reveal the CUL4-DDB1 substrate receptor, WDR23, as both a positive and a negative regulator in cellular stress responses. These opposing roles are mediated by two distinct isoforms: WDR-23A in the cytoplasm and WDR-23B in the nucleus. C. elegans expressing only WDR-23A display activation of SKN-1 and enhanced survival to oxidative stress, whereas animals with restricted WDR-23B expression do not. Additionally, we identify GEN-1, a Holliday junction resolvase, as an evolutionarily conserved WDR-23 substrate and find that the nuclear and cytoplasmic isoforms of WDR-23 differentially affect double-strand break repair. Our results suggest that through differential ubiquitination, nuclear WDR-23B inhibits the activity of substrates, most likely by promoting protein turnover, while cytoplasmic WDR-23A performs a proteasome-independent role. Together, our results establish a cooperative role between two spatially distinct isoforms of WDR-23 in ensuring proper regulation of WDR-23 substrates. |
| 巻・号 | 9(1) |
| ページ | 11783 |
| 公開日 | 2019-8-13 |
| DOI | 10.1038/s41598-019-48286-y |
| PII | 10.1038/s41598-019-48286-y |
| PMID | 31409866 |
| PMC | PMC6692315 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Cell Nucleus / genetics* Cytoplasm / genetics DNA-Binding Proteins / genetics* Gene Expression Regulation / genetics Oxidative Stress / genetics Proteolysis Proteostasis / genetics Repressor Proteins / genetics* Substrate Specificity Transcription Factors / genetics* Ubiquitin-Protein Ligases / genetics* Ubiquitination / genetics |
| IF | 4.011 |
| 引用数 | 0 |
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オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 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 tm2940 |