title: dFOXO Activates Large and Small Heat Shock Protein Genes in Response to Oxidative Stress to Maintain Proteostasis in Drosophila.
abstract: Maintaining protein homeostasis is critical for survival at the cellular and organismal level (Morimoto, R. I. (2011) Cold Spring Harb. Symp. Quant. Biol. 76, 91-99). Cells express a family of molecular chaperones, the heat shock proteins, during times of oxidative stress to protect against proteotoxicity. We have identified a second stress responsive transcription factor, dFOXO, that works alongside the heat shock transcription factor to activate transcription of both the small heat shock protein and the large heat shock protein genes. This expression likely protects cells from protein misfolding associated with oxidative stress. Here we identify the regions of the Hsp70 promoter essential for FOXO-dependent transcription using in vitro methods and find a physiological role for FOXO-dependent expression of heat shock proteins in vivo.
authors.affiliation: From the Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02453.
authors.forename: Marissa R
authors.initials: MR
authors.lastname: Donovan
authors.affiliation: From the Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02453 mmarr@brandeis.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Marr
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D018840:HSP70 Heat-Shock Proteins
keywords: 70-kilodalton heat shock protein (Hsp70); Drosophila; FOXO; oxidative stress; small heat shock protein (sHsp); transcription