Protective Heat Shock

Science's STKE  06 Feb 2001:
Vol. 2001, Issue 68, pp. tw3
DOI: 10.1126/stke.2001.68.tw3

The c-Jun-amino terminal kinases (JNKs) represent a class of mitogen-activated protein kinases (MAPKs) that are activated by cellular stress and can promote apoptosis. Mild heat shock can suppress JNK-stimulated apoptosis. Park et al. showed that Hsp72 could prevent activation of JNK caused by ultraviolet light or transfection with activated upstream JNK kinases, such as MEKK1, and could inhibit JNK activity in vitro. Hsp72 was found to interact physically with JNK by several criteria in vitro and in vivo. This interaction required the peptide-binding domain of Hsp72, not the chaperone activity of Hsp72. Exposure of cells to mild heat shock or transfection of Hsp72 into cells prevented JNK phosphorylation by the JNK kinase SEK1. Antisense experiments confirmed the importance of Hsp72 in the ability of mild heat shock to reduce JNK activation and apoptosis in response to ultraviolet light. Hsp72 appears to be an endogenous inhibitor of the JNK signaling cascade.

H.-S. Park, J.-S. Lee, S.-H. Huh, J.-S. Seo, E.-J. Choi, Hsp72 functions as a natural inhibitory protein of c-Jun-terminal kinase. EMBO J. 20, 446-456 (2001). [Abstract] [Full Text]