title: The phorbol ester 12-O-tetradecanoylphorbol 13-acetate enhances the heat-induced stress response.
abstract: Induction of heat shock gene expression is mediated by specific heat shock transcription factors (HSFs), but the signaling pathways leading to activation of HSFs are poorly understood. To elucidate whether protein kinase C-responsive signaling pathways could be involved in the regulation of heat shock gene expression, we have examined the effects of the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) on the heat-induced stress response in K562 cells. We demonstrate that TPA treatment markedly enhances heat shock gene expression during heat stress, although TPA alone does not induce the heat shock response. This TPA-mediated enhancement can initially be detected as an accelerated acquisition of DNA binding and transcriptional activity of HSF1 resulting in elevated Hsp70 protein concentrations. In the presence of TPA, the attenuation of HSF1 DNA binding activity during continuous exposure to heat shock occurs more rapidly and in concert with the appearance of newly synthesized Hsp70, which supports earlier studies on the autoregulatory role of Hsp70 in deactivation of HSF1. During heat stress, a correlation between the hyperphosphorylation of HSF1 and its transcriptional activity was observed, in both the presence and the absence of TPA. Our results show that the heat-induced stress response can be significantly modulated by activation of protein kinase C-responsive signaling pathways.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Abo Akademi University, FIN-20521 Turku, Finland.
authors.forename: C I
authors.initials: CI
authors.lastname: Holmberg
authors.forename: S
authors.initials: S
authors.lastname: Leppä
authors.forename: J E
authors.initials: JE
authors.lastname: Eriksson
authors.forename: L
authors.initials: L
authors.lastname: Sistonen
mesh_terms: D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D004247:DNA; D013755:Tetradecanoylphorbol Acetate