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dc.contributor.authorMoreno, David F.
dc.contributor.authorJenkins, Kirsten
dc.contributor.authorMorlot, Sandrine
dc.contributor.authorCharvin, Gilles
dc.contributor.authorCsikasz-Nagy, Attila
dc.contributor.authorAldea Malo, Martí
dc.date.accessioned2019-10-25T14:00:03Z
dc.date.available2019-10-25T14:00:03Z
dc.date.issued2019-09-13
dc.identifier.citationMoreno, David F.; Jenkins, Kirsten; Morlot, Sandrine; Charvin, Gilles; Csikasz-Nagy, Attila; Aldea Malo, Martí. «Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1». eLife, 2019, vol. 8, art. e48240. Disponible: <https://elifesciences.org/articles/48240>. Fecha de acceso: 25 oct. 2019. DOI: 10.7554/eLife.48240.034ca
dc.identifier.issn2050-084Xca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/1272
dc.description.abstractLoss of proteostasis and cellular senescence are key hallmarks of aging, but direct cause-effect relationships are not well understood. We show that most yeast cells arrest in G1 before death with low nuclear levels of Cln3, a key G1 cyclin extremely sensitive to chaperone status. Chaperone availability is seriously compromised in aged cells, and the G1 arrest coincides with massive aggregation of a metastable chaperone-activity reporter. Moreover, G1-cyclin overexpression increases lifespan in a chaperone-dependent manner. As a key prediction of a model integrating autocatalytic protein aggregation and a minimal Start network, enforced protein aggregation causes a severe reduction in lifespan, an effect that is greatly alleviated by increased expression of specific chaperones or cyclin Cln3. Overall, our data show that proteostasis breakdown, by compromising chaperone activity and G1-cyclin function, causes an irreversible arrest in G1, configuring a molecular pathway postulating proteostasis decay as a key contributing effector of cell senescence.ca
dc.format.extent27ca
dc.language.isoengca
dc.publishereLife Sciences Publicationsca
dc.relation.ispartofeLifeca
dc.relation.ispartofseries8;
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/ca
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.otherMarques de contrastca
dc.subject.otherHallmarksca
dc.subject.otherMarcas de contrasteca
dc.subject.otherCellsca
dc.subject.otherCélulasca
dc.subject.otherCèl·lulesca
dc.subject.otherCln3ca
dc.titleProteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1ca
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/acceptedVersionca
dc.embargo.termscapca
dc.subject.udc61ca
dc.identifier.doihttps://doi.org/10.7554/eLife.48240.034ca


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