title: Fluorodeoxyuridine enhances the heat shock response and decreases polyglutamine aggregation in an HSF-1-dependent manner in Caenorhabditis elegans.
abstract: The heat shock response (HSR) protects cells from protein-denaturing stress through the induction of chaperones. The HSR is conserved in all organisms and is mediated by the transcription factor HSF-1. We show here that a compound commonly used to prevent larval development in Caenorhabditis elegans, 5-fluoro-2'-deoxyuridine (FUdR), can enhance heat shock induction of hsp mRNA in an HSF-1-dependent manner. Treatment with FUdR can also decrease age-dependent polyglutamine aggregation in a Huntington's disease model, and this effect depends on HSF-1 as well. Therefore, FUdR treatment can modulate the HSR and proteostasis, and should be used with caution when used to inhibit reproduction.
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Brunquell
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Philip
authors.initials: P
authors.lastname: Bowers
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, United States. Electronic address: swesterheide@usf.edu.
authors.forename: Sandy D
authors.initials: SD
authors.lastname: Westerheide
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005467:Floxuridine / Q000494:pharmacology*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects*; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010940:Plant Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D010455:Peptides; D010940:Plant Proteins; D014157:Transcription Factors; D005467:Floxuridine; C097188:polyglutamine
keywords: Caenorhabditis elegans; Fluorodeoxyuridine; HSF-1; Heat shock response; Polyglutamine model; Proteostasis