[HTML][HTML] Transcriptional regulation of the heat shock protein genes by STAT family transcription factors

A Stephanou, DS Latchman - Gene expression, 1999 - ncbi.nlm.nih.gov
A Stephanou, DS Latchman
Gene expression, 1999ncbi.nlm.nih.gov
We have previously demonstrated that interleukin-6 (IL-6) increases the levels of the heat
shock protein 90 (Hsp90) and activates the Hsp90β promoter via the IL-6-activated
transcription factors NF-IL6 and STAT-3. In addition, interferon-γ (IFN-γ) treatment increases
the levels of Hsp70 and Hsp90 and also enhances the activity of the Hsp70 and Hsp90β
promoters with these effects being dependent on activation of the STAT-1 transcription factor
by IFN-γ. The effect of IL-6/STAT-3 and IFN-γ/STAT-1 was mediated via a short region of the …
Abstract
We have previously demonstrated that interleukin-6 (IL-6) increases the levels of the heat shock protein 90 (Hsp90) and activates the Hsp90β promoter via the IL-6-activated transcription factors NF-IL6 and STAT-3. In addition, interferon-γ (IFN-γ) treatment increases the levels of Hsp70 and Hsp90 and also enhances the activity of the Hsp70 and Hsp90β promoters with these effects being dependent on activation of the STAT-1 transcription factor by IFN-γ. The effect of IL-6/STAT-3 and IFN-γ/STAT-1 was mediated via a short region of the Hsp70/Hsp90 promoters, which also mediates the effects of NF-IL6. This region also contains a binding site for the stress-activated transcription factor HSF-1. Furthermore, STAT-1 and HSF-1 interact with one another via a protein-protein interaction and produce a strong activation of transcription. In contrast, STAT-3 and HSF-1 antagonize one another and reduce the activation of both the Hsp70 and Hsp90 promoters. Thus, STAT-1 or STAT-3 activation alone or together results in the activation of Hsp promoters. However, STAT-1 or STAT-3 interact differently with HSF-1 to regulate Hsp promoter activity. These results indicate that STATs are able to moduate the Hsp70 and Hsp90 gene promoters and that these transcription factors are likely to play a very important role in Hsp gene activation by nonstressful stimuli and the intergration of these responses with the stress response of these genes.
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