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

Tran SEF, Annika Meinander, TH Holmström, A Rivero-Muller, KM Heiskanen, EK Linnau, MJ Courtney, DD Mosser, Lea Sistonen, John Eriksson

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    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.
    Original languageUndefined/Unknown
    Pages (from-to)1137–1147
    Number of pages11
    JournalCell Death and Differentiation
    Issue number10
    Publication statusPublished - 2003
    MoE publication typeA1 Journal article-refereed


    • apoptosis
    • caspase
    • CD95
    • death receptor
    • Fas
    • FLIP
    • heat shock
    • stress

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