Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression Journal Article
| Authors: | Kim, D.; Kim, S. H.; Li, G. C. |
| Article Title: | Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression |
| Abstract: | MG132 and lactacystin, two 26S proteasome-specific protease inhibitors, can upregulate heat-shock gene transcription without heat shock. In this study, we showed that both of these inhibitors induce hyperphosphorylation and DNA-binding activity of HSF1 in the absence of heat shock (at 37°C). Since trimerization of HSF1 is known to precede the acquisition of HSF1-DNA binding activity, it seems that MG132- and lactacystin-induced hyperphosphorylation of HSF1 causes conformational changes of HSF1 molecules at 37°C and subsequently triggers its trimerization. Inhibition of protein synthesis by cycloheximide abolished the MG132- or lactacystin-induced hyperphosphorylation and DNA-binding activity of HSF1. These data suggest that the activity of a putative kinase(s) targeting HSF1 is upregulated in the presence of MG132 or lactacystin. The upregulation of the kinase activity requires de novo protein synthesis and is likely due to the inhibition of protein degradation of a short-lived, kinase(s) targeting HSF1 and/or the cofactor(s) for the kinases, through the ubiquitin-proteasome pathway. |
| Keywords: | controlled study; protein expression; protein phosphorylation; dna-binding proteins; nonhuman; ubiquitin; animal cell; mouse; animals; mice; proteasome; proteasome inhibitor; benzyloxycarbonylleucylleucylleucinal; embryo; protein degradation; cell line; drug effect; enzyme activity; cysteine proteinase inhibitors; phosphorylation; transcription factors; transcription regulation; protein synthesis; fibroblasts; receptors, estrogen; heat shock protein 27; heat shock protein 70; conformational transition; dna binding; phosphotransferase; hsp70 heat-shock proteins; wortmannin; protein synthesis inhibition; leupeptins; heat-shock proteins; cycloheximide; staurosporine; acetylcysteine; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; lactacystin; priority journal; article |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 254 |
| Issue: | 1 |
| ISSN: | 0006-291X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 1999-01-08 |
| Start Page: | 264 |
| End Page: | 268 |
| Language: | English |
| DOI: | 10.1006/bbrc.1998.9840 |
| PUBMED: | 9920768 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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