title: Heat-induced expression of the immediate-early gene IER5 and its involvement in the proliferation of heat-shocked cells.
abstract: The serum-inducible and growth factor-inducible gene IER5 encodes a protein that acts as a regulator of cell proliferation. Expression of IER5 is also induced by treatment of cells with ionizing radiation and anticancer agents. In this study, we demonstrate the expression and function of IER5 in heat-shocked cells. Heat treatment causes robust expression of IER5 in a heat shock factor (HSF)1-dependent manner. HSF1 is the master transcriptional regulator of chaperone genes, and the IER5 promoter contains the binding sequence for HSF1 and is bound by heat-activated HSF1. Proteotoxic stressors, such as celastrol and MG132, are known to activate HSF1, and are potent inducers of HSF1 binding and IER5 expression. Overexpression of IER5 leads to upregulation of chaperone gene expression and to an increase in refolding of heat-denatured proteins. Cells expressing IER5 efficiently recover viability after heat challenge. These observations suggest that HSF1-mediated IER5 expression is involved in the expression of chaperone genes and in recovery from thermal stress.
authors.affiliation: Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D007976:Leupeptins / Q000008:administration & dosage; D018832:Molecular Chaperones / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D053978:Pentacyclic Triterpenes; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014315:Triterpenes / Q000008:administration & dosage
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; C118926:IER5 protein, human; D017874:Immediate-Early Proteins; D007976:Leupeptins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D014157:Transcription Factors; D014315:Triterpenes; C050414:celastrol; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: HSF1; IER5; chaperone; heat shock response; immediate-early gene