10.1371\/journal.pgen.1002299<\/a><\/p>\nAuthors:<\/h4>\n
Andr\u00e9s Mansisidor, Germano Cecere, Sebastian Hoersch, Morten B. Jensen, Trupti Kawli, Lisa M. Kennedy, Violeta Ch\u00e1vez, Man\u2010Wah Tan, Jason D. Lieb, Alla Grishok<\/p>\n
Abstract:<\/h4>\n
<div><p>Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16\/FOXO and SKN-1\/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in <i>Caenorhabditis elegans<\/i>, we identified an important role for these factors in the negative modulation of transcription of the insulin\/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of <i>pdk-1<\/i> in <i>zfp-1<\/i> and <i>rde-4<\/i> mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating <i>pdk-1<\/i> transcription was important for the extended lifespan of the <i>age-1(hx546)<\/i> reduction-of-function PI3 kinase mutant, since the lifespan of the <i>age-1; zfp-1<\/i> double mutant strain was significantly shorter compared to <i>age-1(hx546)<\/i>. We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16\u2013dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.<\/p><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"
DOI: 10.1371\/journal.pgen.1002299 Authors: Andr\u00e9s Mansisidor, Germano Cecere, Sebastian Hoersch, Morten B. Jensen, Trupti Kawli, Lisa M. Kennedy, Violeta Ch\u00e1vez, Man\u2010Wah Tan, Jason D. Lieb, Alla Grishok Abstract: <div><p>Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16\/FOXO and SKN-1\/Nrf transcription […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-1078","post","type-post","status-publish","format-standard","hentry","category-blurev-rde-rrde"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/1078","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1078"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/1078\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1078"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1078"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1078"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}