Surviving the Heat

Science's STKE  29 Aug 2000:
Vol. 2000, Issue 47, pp. tw11
DOI: 10.1126/stke.2000.47.tw11

Mild heat shock can allow cells to survive a subsequently more severe heat stress. Gabai et al. show that mild heat shock induces the heat shock protein Hsp72 . The increase in Hsp72 is required for thermotolerance and the ability to survive normally nontoxic heat stress in fibroblasts is impaired if Hsp72 expression is blocked by expression of Hsp72 antisense RNA. Whereas many protein kinases, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase (JNK), are activated by heat shock, during subsequent heat stress, JNK activity is suppressed in thermotolerant cells. Pharmacological analysis or expression of dominant-negative proteins suggested that activation of ERK1/2 and Akt promoted cell survival following heat shock but that inhibition of JNK was associated with cell survival. Overexpression of Hsp72 led to a suppression of JNK activation and increased cell survival following mild heat shock and inhibition of Hsp72 with antisense RNA led to prolonged JNK activation and decreased viability.

Gabai, V.L., Yaglom, J.A., Volloch, V., Meriin, A.B., Force, T., Koutroumanis, M., Massie, B., Mosser, D.D., and Sherman, M.Y. (2000) Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in development of tolerance to caspase-independent cell death. Mol. Cell. Biol. 20: 6826-6836. [Abstract] [Full Text]