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Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response

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dc.contributor.author Truttmann, Matthias C.
dc.contributor.author Zheng, Xu
dc.contributor.author Hanke, Leo
dc.contributor.author Damon, Jadyn R.
dc.contributor.author Grootveld, Monique
dc.contributor.author Krakowiak, Joanna
dc.contributor.author Pincus, David
dc.contributor.author Ploegh, Hidde
dc.date.accessioned 2017-09-13T19:50:57Z
dc.date.available 2017-09-13T19:50:57Z
dc.date.issued 2016-12
dc.date.submitted 2016-07
dc.identifier.issn 0027-8424
dc.identifier.issn 1091-6490
dc.identifier.uri http://hdl.handle.net/1721.1/111201
dc.description.abstract Protein 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.iso en_US
dc.publisher National Academy of Sciences (U.S.) en_US
dc.relation.isversionof http://dx.doi.org/10.1073/pnas.1619234114 en_US
dc.rights Article 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.source PNAS en_US
dc.title Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response en_US
dc.type Article en_US
dc.identifier.citation Truttmann, 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 Sciences en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.mitauthor Ploegh, Hidde
dc.relation.journal Proceedings of the National Academy of Sciences en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Truttmann, Matthias C.; Zheng, Xu; Hanke, Leo; Damon, Jadyn R.; Grootveld, Monique; Krakowiak, Joanna; Pincus, David; Ploegh, Hidde L. en_US
dspace.embargo.terms N en_US
dc.identifier.orcid https://orcid.org/0000-0002-1090-6071


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