Fas-activation inhibits activation of heat shock factor (hsF)-1 and expression of heat shock protein (hsp) 70

Activation of heat shack factor (HSF)-1 DNA binding and heat shock protein (hsp)-70 expression enable resistance of cells to various farms of stress a nd maintain cell survival. Fas, a membrane-bound protein, is a central pro- apoptotic factor. Its activation leads to a cascade of events resulting in programmed cell death. Herein, these two mechanisms with contrary functions , promoting either cell survival or death, were addressed for their potenti al to inhibit each other's activation. Induction of Fas-mediated signalling was followed by a rapid decrease of HSF1 DNA binding and inducible hsp70 e xpression. Inhibition of HSF1 DNA binding was demonstrated to be based on a bsent hyperphosphorylation of HSF1 during FAS-signalling. These effects of Fas-activation on the HSF1/hsp70 stress response were blocked by ICE (caspa se 1)-inhibitors, suggesting an ICE-mediated process. Furthermore, inhibiti on of HSF1/hsp70 was accompanied by an increase of apoptosis rates from 20 % to 50 % in response to heat stress. When analyzing Fas-mediated apoptosis in the presence of HSF1/hsp70 activation, decreased apoptosis rates were d etected with induced expression of hsp70 but not with activation of HSF1-DN A binding alone. Thus, we conclude that inhibition of the HSF1/hsp70 stress response during Fas-mediated apoptosis and vice versa may facilitate a cel l to pass a previously choosen pathway, stress resistance or apoptosis.