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dc.contributor.authorTruttmann, Matthias C.
dc.contributor.authorZheng, Xu
dc.contributor.authorHanke, Leo
dc.contributor.authorDamon, Jadyn R.
dc.contributor.authorGrootveld, Monique
dc.contributor.authorKrakowiak, Joanna
dc.contributor.authorPincus, David
dc.contributor.authorPloegh, Hidde
dc.date.accessioned2017-09-13T19:50:57Z
dc.date.available2017-09-13T19:50:57Z
dc.date.issued2016-12
dc.date.submitted2016-07
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/111201
dc.description.abstractProtein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes—huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively—in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality. Overexpression of Ssa2, a cytosolic heat shock protein (Hsp)70, was sufficient to partially rescue growth. In human cell lines, overexpression of active HYPE similarly induced protein aggregation and the HSF1-dependent heat shock response. Excessive AMPylation also abolished HSP70-dependent influenza virus replication. Our findings suggest a mode of Hsp70 inactivation by AMPylation and point toward a role for protein AMPylation in the regulation of cellular protein homeostasis beyond the endoplasmic reticulum.en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1619234114en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleUnrestrained AMPylation targets cytosolic chaperones and activates the heat shock responseen_US
dc.typeArticleen_US
dc.identifier.citationTruttmann, Matthias C. et al. “Unrestrained AMPylation Targets Cytosolic Chaperones and Activates the Heat Shock Response.” Proceedings of the National Academy of Sciences 114, 2 (January 2017): E152–E160 © 2017 National Academy of Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorPloegh, Hidde
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsTruttmann, Matthias C.; Zheng, Xu; Hanke, Leo; Damon, Jadyn R.; Grootveld, Monique; Krakowiak, Joanna; Pincus, David; Ploegh, Hidde L.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-1090-6071
mit.licensePUBLISHER_POLICYen_US


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