HSP72 can protect cells from heat-induced apoptosis by accelerating the inactivation of stress kinase JNK

The major heat shock protein Hsp72 prevents heat-induced apoptosis. We have previously demonstrated that transiently expressed Hsp72 exerts its anti-a poptotic effect by suppressing the activity of stress-kinase JNK, an early component of the apoptotic pathway initiated by heat shock. On the other ha nd, constitutive expression of Hsp72 does not lead to suppression of heat-i nduced JNK activation, yet still efficiently prevents apoptosis. To address this apparent contradiction, we studied the effects of constitutively expr essed Hsp72 on activation of JNK and apoptosis in Rat-1 fibroblasts. We fou nd that the level of heat-induced apoptosis directly correlated with the du ration rather than the magnitude of JNK activity following heat shock. Cons titutively expressed Hsp72 strongly reduced the duration of JNK while it di d not suppress initial JNK activation. These effects were due to Hsp72-medi ated acceleration of JNK dephosphorylation. Addition of vanadate to inhibit JNK phosphatase activity completely prevented the anti-apoptotic action of Hsp72. Therefore, suppression of heat-induced apoptosis by Hsp72 could be fully accounted for by its effects on JNK activity.