p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans

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p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans

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dc.contributor.author Troemel, Emily R
dc.contributor.author Chu, Stephanie W
dc.contributor.author Reinke, Valerie
dc.contributor.author Kim, Dennis H
dc.contributor.author Lee, Siu Sylvia
dc.contributor.author Ausubel, Frederick M.
dc.date.accessioned 2010-11-01T17:48:45Z
dc.date.issued 2006
dc.identifier.citation Troemel, Emily R., Stephanie W. Chu, Valerie Reinke, Siu Sylvia Lee, Frederick M. Ausubel, Dennis H. Kim. 2006. p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans. PLoS Genetics 2:e183. en_US
dc.identifier.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4515095
dc.description.abstract The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2–DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of daf-2 mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of daf-2 mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2–DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of daf-2 mutants suggests that innate immunity is an important determinant of longevity. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.0020183 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635533/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject infectious diseases en_US
dc.subject genetics en_US
dc.subject functional genomics en_US
dc.subject disease models en_US
dc.subject gene expression en_US
dc.subject nematodes en_US
dc.subject eubacteria en_US
dc.title p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Ausubel, Frederick M.
dc.date.available 2010-11-01T17:48:45Z

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  • FAS Scholarly Articles [7362]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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