Heat stress downregulates FLIP and sensitizes cells to Fas receptor-mediated apoptosis

• DOI: 10.1038/sj.cdd.4401278
• Publication Date: 2003-09-19T08:43:54Z
• Authors: S E F Tran; A Meinander; T H Holmström; A Rivero-Müller; K M Heiskanen; E K Linnau; M J Courtney; D D Mosser; L Sistonen; J E Eriksson
• Keywords: Jurkat cells; Flip; UVB-induced apoptosis; Caspase 8

The heat shock response and death receptor-mediated apoptosis are both key physiological determinants of cell survival. We found that exposure to a mild heat stress rapidly sensitized Jurkat and HeLa cells to Fas-mediated apoptosis. We further demonstrate that Hsp70 and the mitogen-activated protein kinases, critical molecules involved in both stress-associated and apoptotic responses, are not responsible for the sensitization. Instead, heat stress on its own induced downregulation of FLIP and promoted caspase-8 cleavage without triggering cell death, which might be the cause of the observed sensitization. Since caspase-9 and -3 were not cleaved after heat shock, caspase-8 seemed to be the initial caspase activated in the process. These findings could help understanding the regulation of death receptor signaling during stress, fever, or inflammation.