Hsp72 : (a natural inhibitor of the stress-activated signaling)

다국어 초록 (Multilingual Abstract)

Hsp72, a major inducible member of the heat shock protein family, has been shown to protect cells against many cellular stresses including heat shock and ischemia. In our present study, we observed that mild heat shock suppressed both c-Jun N-terminal kinase 1(JNK1) and p38 activity. Constitutively overexpressed Hsp72 also inhibited UV-induced JNK1 and p38 activation in NIH/3T3 cells. Both in vitro binding and kinase studies indicated that Hsp72 physically interacted with JNK1 and that the peptide-binding domain of Hsp72 might be involved in the binding and inhibition of JNK1. In vivo binding between endogenous Hsp72 and JNK1 protein in NIH/3T3 cells was confirmed by co-immunoprecipitation. Constitutively overexpressed Hsp72 also inhibited the JNK-dependent stimulation of c-Jun-mediated luciferase reporter activity and the apoptotic cell death induced by MEKK1 activation. Hsp72 antisense oligonucleotides blocked Hsp72 production in NIH/3T3 cells in response to mild heat shock and concomitantly abolished the suppressive effect of mild heat shock on UV-induced JNK activation and apoptosis. Taken together, our data strongly suggest that Hsp72 can modulate stress-activated signaling.