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

: Tran SEF, Meinander A, Holmstrom TH, Rivero-Muller A, Heiskanen KM, Linnau EK, Courtney MJ, Mosser DD, Sistonen L, Eriksson JE

Publisher: NATURE PUBLISHING GROUP

: 2003

: Cell Death and Differentiation

: CELL DEATH AND DIFFERENTIATION

: CELL DEATH DIFFER

: 10

: 1137

: 1147

: 11

: 1350-9047

DOI: https://doi.org/10.1038/sj.cdd.4401278

: https://www.nature.com/articles/4401278

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.