TY - JOUR
T1 - The phorbol ester 12-O-tetradecanoylphorbol 13-acetate enhances the heat-induced stress response
AU - Holmberg, C I
AU - Leppä, S
AU - Eriksson, J E
AU - Sistonen, L
PY - 1997/3/7
Y1 - 1997/3/7
N2 - 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.
AB - 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.
KW - DNA/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Gene Expression Regulation/drug effects
KW - HSP70 Heat-Shock Proteins/genetics
KW - HSP90 Heat-Shock Proteins/genetics
KW - HeLa Cells
KW - Heat Shock Transcription Factors
KW - Heat-Shock Response/drug effects
KW - Humans
KW - Phosphorylation
KW - Tetradecanoylphorbol Acetate/pharmacology
KW - Time Factors
KW - Transcription Factors
KW - Tumor Cells, Cultured
U2 - 10.1074/jbc.272.10.6792
DO - 10.1074/jbc.272.10.6792
M3 - Article
C2 - 9045713
SN - 0021-9258
VL - 272
SP - 6792
EP - 6798
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 10
ER -