Protein misfolding is implicated in neurodegenerative diseases and occurs in aging. However, the contribution of the misfolded ensembles to toxicity remains largely unknown. Here we introduce 2 primate cell models of destabilized proteins devoid of specific cellular functions and interactors, as bona fide misfolded proteins, allowing us to isolate the gain-of-function of non-native structures. Both GFP-degron and a mutant chloramphenicol-acetyltransferase fused to GFP (GFP-Δ9CAT) form perinuclear aggregates, are degraded by the proteasome, and colocalize with and induce the chaperone Hsp70 (HSPA1A/B) in COS-7 cells. We find that misfolded proteins neither significantly compromise chaperone-mediated folding capacity nor induce cell death. However, they do induce growth arrest in cells that are unable to degrade them and promote stress-induced death upon proteasome inhibition by MG-132 and heat shock. Finally, we show that overexpression of all heat-shock factor-1 (HSF1) and Hsp70 proteins, as well as wild-type and deacetylase-deficient (H363Y) SIRT1, rescue survival upon stress, implying a noncatalytic action of SIRT1 in response to protein misfolding. Our study establishes a novel model and extends our knowledge on the mechanism of the function-independent proteotoxicity of misfolded proteins in dividing cells.—Arslan, M. A., Chikina, M., Csermely, P., Sőti, C. Misfolded proteins inhibit proliferation and promote stress-induced death in SV40-transformed mammalian cells. HSF1 Hsp70 sirtuin Footnotes This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Received May 11, 2011. Accepted October 20, 2011. © FASEB Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print November 2, 2011 , doi: 10.1096/fj.11-186197 February 2012 The FASEB Journal vol. 26 no. 2 766-777 » Abstract Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.11-186197v1 26/2/766 most recent Classifications Research Communications Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Arslan, M. A. Articles by Sőti, C. PubMed PubMed citation Articles by Arslan, M. A. Articles by Sőti, C. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 26 (2) Alert me to new issues of The FASEB Journal Submit Manuscripts Online Press Room Information for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Activate Online View Collected Papers Breakthroughs in Bioscience Advertising Copyright Permissions Feedback Subscribe to RSS FASEB Publication Services Go to FASEB Online Copyright © 2012 by the Federation of American Societies for Experimental Biology Print ISSN: 0892-6638 Online ISSN: 1530-6860 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23107677-1"); pageTracker._trackPageview();

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