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Articles by Chi K. Leung in JoVE
Floresan ile yüksek verim Tarama ve Biyoalgılayıcı C. elegans Suşlarının
Chi K. Leung1, Andrew Deonarine1, Kevin Strange2, Keith P. Choe1
1Department of Biology, University of Florida, 2Mount Desert Island Biological Laboratory
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Other articles by Chi K. Leung on PubMed
Depletion of a Nucleolar Protein Activates Xenobiotic Detoxification Genes in Caenorhabditis Elegans Via Nrf /SKN-1 and P53/CEP-1
Free Radical Biology & Medicine. Mar, 2012 | Pubmed ID: 22240150
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.