A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling

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dc.contributor.authorPark, Hae-Eun H.ko
dc.contributor.authorHwang, Wooseonko
dc.contributor.authorHam, Seokjinko
dc.contributor.authorKim, Eunahko
dc.contributor.authorAltintas, Ozlemko
dc.contributor.authorPark, Sangsoonko
dc.contributor.authorSon, Heehwa G.ko
dc.contributor.authorLee, Yujinko
dc.contributor.authorLee, Dongyeopko
dc.contributor.authorHeo, Won Doko
dc.contributor.authorLee, Seung-Jae, Vko
dc.date.accessioned2021-10-11T04:30:19Z-
dc.date.available2021-10-11T04:30:19Z-
dc.date.created2021-10-11-
dc.date.created2021-10-11-
dc.date.created2021-10-11-
dc.date.issued2021-09-
dc.identifier.citationNATURE COMMUNICATIONS, v.12, no.1-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10203/288119-
dc.description.abstractInsulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans, mutations in the daf-2/insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, and reproduction. Whether these pleiotropic effects can be dissociated at a specific step in insulin/IGF-1 signaling pathway remains unknown. Through performing a mutagenesis screen, we identified a missense mutation daf-18(yh1) that alters a cysteine to tyrosine in DAF-18/PTEN phosphatase, which maintained the long lifespan and enhanced immunity, while improving the reduced motility in adult daf-2 mutants. We showed that the daf-18(yh1) mutation decreased the lipid phosphatase activity of DAF-18/PTEN, while retaining a partial protein tyrosine phosphatase activity. We found that daf-18(yh1) maintained the partial activity of DAF-16/FOXO but restricted the detrimental upregulation of SKN-1/NRF2, contributing to beneficial physiological traits in daf-2 mutants. Our work provides important insights into how one evolutionarily conserved component, PTEN, can coordinate animal health and longevity. Mutations in daf-2/insulin/IGF-1 receptor impair the growth and reproduction of C. elegans but conversely enhance immunity and lifespan. Here, the authors show that a missense mutation in the gene retains the effects on lifespan and immunity and improves motility.-
dc.languageEnglish-
dc.publisherNATURE PORTFOLIO-
dc.titleA PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling-
dc.typeArticle-
dc.identifier.wosid000698984500004-
dc.identifier.scopusid2-s2.0-85115688317-
dc.type.rimsART-
dc.citation.volume12-
dc.citation.issue1-
dc.citation.publicationnameNATURE COMMUNICATIONS-
dc.identifier.doi10.1038/s41467-021-25920-w-
dc.contributor.localauthorHeo, Won Do-
dc.contributor.localauthorLee, Seung-Jae, V-
dc.contributor.nonIdAuthorPark, Hae-Eun H.-
dc.contributor.nonIdAuthorHwang, Wooseon-
dc.contributor.nonIdAuthorHam, Seokjin-
dc.contributor.nonIdAuthorKim, Eunah-
dc.contributor.nonIdAuthorAltintas, Ozlem-
dc.contributor.nonIdAuthorPark, Sangsoon-
dc.contributor.nonIdAuthorSon, Heehwa G.-
dc.contributor.nonIdAuthorLee, Yujin-
dc.contributor.nonIdAuthorLee, Dongyeop-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusPROTEIN PHOSPHATASE-ACTIVITY-
dc.subject.keywordPlusTUMOR-SUPPRESSOR PTEN-
dc.subject.keywordPlusC-ELEGANS-
dc.subject.keywordPlusSTRESS RESISTANCE-
dc.subject.keywordPlusDAUER FORMATION-
dc.subject.keywordPlusREGULATES LONGEVITY-
dc.subject.keywordPlusFACTOR SKN-1-
dc.subject.keywordPlusLIFE-SPAN-
dc.subject.keywordPlusMUTATION-
dc.subject.keywordPlusDAF-16-
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