title: Conventional and novel PKC isoenzymes modify the heat-induced stress response but are not activated by heat shock.
abstract: In mammalian cells, the heat-induced stress response is mediated by the constitutively expressed heat shock transcription factor 1 (HSF1). Upon exposure to elevated temperatures, HSF1 undergoes several post-translational modifications, including inducible phosphorylation or hyperphosphorylation. To date, neither the role of HSF1 hyperphosphorylation in regulation of the transcriptional activity of HSF1 nor the signaling pathways involved have been characterized. We have previously shown that the protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), markedly enhances the heat-induced stress response, and in the present study we elucidate the mechanism by which PKC activation affects the heat shock response in human cells. Our results show that several conventional and novel PKC isoenzymes are activated during the TPA-mediated enhancement of the heat shock response and that the enhancement can be inhibited by the specific PKC inhibitor bisindolylmaleimide I. Furthermore, the potentiating effect of TPA on the heat-induced stress response requires an intact heat shock element in the hsp70 promoter, indicating that PKC-responsive pathways are able to modulate the activity of HSF1. We also demonstrate that PKC is not activated by heat stress per se. These results reveal that PKC exhibits a significant modulatory role of the heat-induced stress response, but is not directly involved in regulation of the heat shock response.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Abo Akademi University, PO Box 123, FIN-20521 Turku, Finland.
authors.forename: C I
authors.initials: CI
authors.lastname: Holmberg
authors.forename: P M
authors.initials: PM
authors.lastname: Roos
authors.forename: J M
authors.initials: JM
authors.lastname: Lord
authors.forename: J E
authors.initials: JE
authors.lastname: Eriksson
authors.forename: L
authors.initials: L
authors.lastname: Sistonen
mesh_terms: D002273:Carcinogens / Q000494:pharmacology; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute; D008301:Maleimides / Q000494:pharmacology; D019913:Nuclear Localization Signals; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D019913:Nuclear Localization Signals; D012333:RNA, Messenger; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate