Activation of Fas inhibits heat-induced activation of HSF1 and up-regulation of hsp70

被引:68
作者
Schett, G
Steiner, CW
Gröger, M
Winkler, S
Graninger, W
Smolen, J
Xu, QB
Steiner, G
机构
[1] Univ Vienna, Div Rheumatol, Dept Internal Med 3, A-1090 Vienna, Austria
[2] Univ Vienna, Dept Immunodermatol, A-1090 Vienna, Austria
[3] Univ Vienna, Div Infectiol, Dept Internal Med 1, A-1090 Vienna, Austria
[4] Austrian Acad Sci, Inst Biomed Aging Res, Innsbruck, Austria
[5] Ludwig Boltzmann Inst Rheumatol & Balneol, Vienna, Austria
关键词
Fas activation; antibody; heat shock element; apoptosis hsp;
D O I
10.1096/fasebj.13.8.833
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of heat shock factor (HSF) 1-DNA binding and inducible heat shock protein (hsp) 70 (also called hsp72) expression enables cells to resist various forms of stress and survive. Fas, a membrane-bound protein, is a central proapoptotic factor; its activation leads to a cascade of events, resulting in programmed cell death. These two mechanisms with contradictory functions, promoting either cell survival or death, were examined for their potential to inhibit each other's activation. Induction of FAS-mediated signaling was followed by a rapid decrease in HSF1-DNA binding and inducible hsp70 expression. Inhibition of HSF1-DNA binding was demonstrated to be based on absent hyperphosphorylation of HSF1 during FAS signaling. These effects of FAS activation on the HSF1/hsp70 stress response were blocked by ICE (caspase 1) inhibitors, suggesting an ICE-mediated process. Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase in apoptosis rates from 20% to 50% in response to heat stress. When analyzing the effects of HSF1/hsp70 activation on Fas-mediated apoptosis, protection from apoptosis was seen in cells with induced hsp70 protein levels, but not in cells that were just induced for HSF1-DNA binding. Thus, we conclude that inhibition of HSF1/hsp70 stress response during Fas-mediated apoptosis and vice versa may facilitate a cell. to pass a previously chosen pathway, stress resistance or apoptosis, without the influence of inhibitory signals.
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页码:833 / 842
页数:10
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