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Genome-wide screening identifies new genes required for stress-induced phase 2 detoxification gene expression in animals

Overview of attention for article published in BMC Biology, August 2014
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  • High Attention Score compared to outputs of the same age and source (81st percentile)

Mentioned by

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4 tweeters
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1 patent

Citations

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19 Dimensions

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51 Mendeley
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Title
Genome-wide screening identifies new genes required for stress-induced phase 2 detoxification gene expression in animals
Published in
BMC Biology, August 2014
DOI 10.1186/s12915-014-0064-6
Pubmed ID
Authors

Helen M Crook-McMahon, Monika Oláhová, Emma L Button, Johnathan J Winter, Elizabeth A Veal

Abstract

BackgroundPhase 2 detoxification enzymes provide a vital defense against reactive oxygen species, including xenobiotic metabolites, that cause oxidative damage involved in drug toxicity and many diseases. Hence, there is great interest in understanding how levels of these enzymes are regulated. CnC transcription factors, such as mammalian Nrf2, drive the expression of phase 2 enzymes and are activated as an important conserved response to oxidative stress and xenobiotics. For instance, the Caenorhabditis elegans Nrf2 ortholog, SKN-1, is activated in response to arsenite by the stress-activated p38-related kinase, PMK-1, leading to increased expression of phase 2 enzymes. Here we have used a genome-wide screening approach to identify other C. elegans genes that are required for stress-induced increases in phase 2 detoxification gene expression.ResultsTaking advantage of the elevated phase 2 gene expression in a mutant lacking the peroxidase PRDX-2, we have identified many new genes that are required for stress-induced expression of gcs-1, a phase 2 enzyme critically required for glutathione synthesis. Significantly, these include genes previously implicated in resistance to ionizing radiation, longevity, and responses to pathogenic infection. Many of these new candidate activators of gcs-1 are also required for the stress-induced intestinal expression of other phase 2 genes. However, intriguingly, our data suggest other factors may be specifically required for the stress-induced expression of gcs-1. Notably, we demonstrate that the candidate activator TIR-1(SARM1) and the MAPKKK NSY-1(Ask1) are required for the arsenite-induced activation of PMK-1. However, our data suggest that the majority of candidates participate in novel mechanisms to promote gcs-1 expression. For example, the E4 ubiquitin ligase UFD-2(UBE4B) is dispensable for PMK-1 activation but important for maintaining nuclear levels of SKN-1, the stress-induced expression of multiple SKN-1-target genes and oxidative stress resistance.ConclusionsHere we present the first functional, genome-wide analysis identifying genes that are required for activation of phase 2 detoxification genes in an animal. Our study identifies potential new regulators of Nrf2; reveals that additional mechanisms promote the stress-induced expression of specific phase 2 detoxification genes; and provides new insight into the relationships between these universally important stress defenses, oxidative stress resistance and aging.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 4%
Germany 1 2%
Unknown 48 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 33%
Researcher 9 18%
Student > Doctoral Student 5 10%
Professor > Associate Professor 4 8%
Student > Master 3 6%
Other 10 20%
Unknown 3 6%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 41%
Biochemistry, Genetics and Molecular Biology 15 29%
Neuroscience 2 4%
Environmental Science 1 2%
Immunology and Microbiology 1 2%
Other 3 6%
Unknown 8 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 July 2020.
All research outputs
#4,923,968
of 18,156,586 outputs
Outputs from BMC Biology
#982
of 1,569 outputs
Outputs of similar age
#53,328
of 217,181 outputs
Outputs of similar age from BMC Biology
#3
of 11 outputs
Altmetric has tracked 18,156,586 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,569 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.1. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 217,181 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.