Involvement of c-Jun NH2-Terminal Kinase Pathway in Differential Regulation of Heat Shock Proteins by Anticancer Drugs

In the present study, we examined the modulation of heat shock factor 1 (HSF1) activity and expression of heat shock proteins (HSPs) after exposure to anticancer drugs. Anticancer drugs induced HSF1 DNA-binding activity, and this was followed by an increase of mitochondrial HSP75 and HSP60 levels an...

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Published in:Biochemical and biophysical research communications 1999-08, Vol.262 (2), p.516-522
Main Authors: Kim, Sun Hee, Kim, Dooha, Jung, Gyoo Sik, Um, Jee Hyun, Chung, Byung Seon, Kang, Chi Dug
Format: Article
Language:English
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Summary:In the present study, we examined the modulation of heat shock factor 1 (HSF1) activity and expression of heat shock proteins (HSPs) after exposure to anticancer drugs. Anticancer drugs induced HSF1 DNA-binding activity, and this was followed by an increase of mitochondrial HSP75 and HSP60 levels and concurrent decrease of cytoplasmic HSP70 levels. Unlike heat shock-induced full phosphorylation, HSF1 was partially phosphorylated after exposure to vincristine, and this result was tightly correlated with the kinetics of JNK/SAPK activation, and up-regulation of mitochondrial HSP75 level and concurrent down-regulation of HSP70. Furthermore, the dominant-negative mutant of SEK1 blocked the phosphorylation of HSF1 and up-regulation of mitochondrial HSP75 in response to vincristine or vinblastine. These data suggest that anticancer drugs regulate the HSF1 transcriptional activity differently from heat shock, and JNK/SAPK pathway appears to be involved in anticancer drug-induced HSF1 phosphorylation and consequently differential regulation of mitochondrial HSP75 and HSP60 and cytoplasmic HSP70.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.1229