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 was previously attributed to its ability to prevent aggregation and to accelerate refolding of damaged proteins. This repair function of Hsp72 may play an important role in cell survival after extremely harsh protein 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. some genotoxic agents. These stresses kill cells through activation of apoptosis, and Hsp72 increases cell survival by interfering with the apoptotic program. Recently it has been found that Hsp72 mediates suppression 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 can explain increased stress sensitivity of aged cells in which compromised inducibility of Hsp72 leads to a loss of control of JNK activation by stresses and subsequently to a higher rate of apoptotic death.
Gabai
V L
VL
Boston Biomedical Research Institute, MA, USA.
Meriin
A B
AB
Yaglom
J A
JA
Volloch
V Z
VZ
Sherman
M Y
MY
D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases
D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases