ROLE OF HSP70 IN REGULATION OF STRESS-KINASE JNK - IMPLICATIONS IN APOPTOSIS AND AGING

Cell protection from stresses by the major heat shock protein Hsp72 wa s previously attributed to its ability to prevent aggregation and to a ccelerate refolding of damaged proteins. This repair function of Hsp72 may play an important role in cell survival after extremely harsh pro tein damaging treatments leading to necrotic cell death. On the other hand, protein repair function of Hsp72 cannot explain how it protects cells from stresses which do not cause direct protein damage, e.g. som e genotoxic agents. These stresses kill cells through activation of ap optosis, and Hsp72 increases cell survival by interfering with the apo ptotic program. Recently it has been found that Hsp72 mediates suppres sion of a stress-activated protein kinase, JNK, an early component of stress-induced apoptotic signalling pathway. This finding provides the basis for the anti-apoptotic activity of Hsp72. These observations ca n explain increased stress sensitivity of aged cells in which compromi sed inducibility of Hsp72 leads to a loss of control of JNK activation by stresses and subsequently to a higher rate of apoptotic death. (C) 1998 Federation of European Biochemical Societies.