| 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
|
| リソース情報 |
| 線虫 |
BY4544 |
