ATPase activity of the heat shock protein Hsp72 is dispensable for its effects on dephosphorylation of stress kinase JNK and on heat-induced apoptosis

ri major inducible heat shock protein, Hsp72, has previously been found to stimulate dephosphorylation (inactivation) of stress kinase JNK in heat-sho cked cells and protect them from apoptasis, Using Rat-1 fibroblasts with co nstitutive expression of a human Hsp72 or its deletion mutant lacking an AT Pase domain (C-terminal fragment (CTF)), me tested whether ATPase activity of Hsp72 is necessary for these effects. We found that expression of CTF ma rkedly increased, similarly to the intact protein, JNK dephosphorylation in heat-shocked cells, As a result, JNK inactivation following heat shock occ urred much faster in cells expressing either full-length or mutant Hsp72 th an in parental cells and this,vas accompanied by suppression of heat-induce d apoptosis, Thus, protein refolding activity of Hsp72 appears to he dispen sable for its effect on JNK inactivation and apoptosis. (C) 1999 Federation of European Biochemical Societies.