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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Tran SEF, Meinander A, Holmström TH, Rivero-Muller A, Heiskanen KM, Linnau EK, Courtney MJ, Mosser DD, Sistonen L, Eriksson JE
Publication year: 2003
Journal: Cell Death and Differentiation
Journal acronym: CELL DEATH DIFFER
Volume number: 10
Issue number: 10
Start page: 1137
End page: 1147
Number of pages: 11
ISSN: 1350-9047
eISSN: 1476-5403


Abstract

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.


Keywords

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

Last updated on 2019-13-12 at 04:04

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