論文 - 詳細
| RRC ID | 16004 |
|---|---|
| 著者 | Leung CK, Empinado H, Choe KP. |
| タイトル | Depletion of a nucleolar protein activates xenobiotic detoxification genes in Caenorhabditis elegans via Nrf /SKN-1 and p53/CEP-1. |
| ジャーナル | Free Radic Biol Med |
| Abstract |
The nucleolus has recently emerged as a major coordinator of cellular stress responses by regulating the tumor suppressor p53. However, it is not known if the nucleolus regulates the cap 'n' collar (CnC) transcription factors SKN-1 and Nrf2, which activate conserved antioxidant and detoxification responses in C. elegans and mammals, respectively. A screen for negative regulators of detoxification genes in C. elegans identified the conserved WD40 repeat containing protein WDR-46. This protein is highly conserved with yeast UTP7, which functions in 18S rRNA processing and assembly of the 40S small ribosomal subunit. WDR-46 is expressed in the nucleoli of multiple tissues in C. elegans and is required for rRNA processing. Mutation or silencing of WDR-46 activates the single C. elegans CnC homologue SKN-1 and increases expression of its target genes. Depletion of wdr-46 reduces lifespan and stress resistance and SKN-1 partially compensates. Lastly, the C. elegans p53 homologue CEP-1 is partially required for activation of gst-4 when wdr-46 or other ribosome processing genes are silenced but not when translation initiation genes are silenced suggesting that disruptions to nucleolar function can activate SKN-1 by a mechanism that involves p53/cep-1 and is independent of protein translation. |
| 巻・号 | 52(5) |
| ページ | 937-50 |
| 公開日 | 2012-3-1 |
| DOI | 10.1016/j.freeradbiomed.2011.12.009 |
| PII | S0891-5849(11)01253-6 |
| PMID | 22240150 |
| MeSH | Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Nucleolus / metabolism DNA-Binding Proteins / metabolism* Forkhead Transcription Factors Gene Expression Gene Expression Regulation Glutathione Transferase / genetics Glutathione Transferase / metabolism Inactivation, Metabolic / genetics* Life Expectancy Nuclear Proteins / deficiency Nuclear Proteins / genetics* Nuclear Proteins / metabolism Promoter Regions, Genetic RNA Processing, Post-Transcriptional RNA, Messenger / metabolism RNA, Ribosomal / metabolism Stress, Physiological Transcription Factors / metabolism* Tumor Suppressor Protein p53 / metabolism* Xenobiotics / metabolism* |
| IF | 6.17 |
| 引用数 | 12 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR 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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| 各媒体での言及数の合計 | 0 |
| 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 | BY4544 |