Role of the heat shock response and molecular chaperones in oncogenesis and cell death

Exposure of cells to conditions of environmental stress-including heat shoc k, oxidative stress, heavy metals, or pathologic conditions, such as ischem ia and reperfusion, inflammation, tissue damage, infection, and mutant prot eins associated with genetic diseases-results in the inducible expression o f heat shock proteins that function as molecular chaperones or proteases, M olecular chaperones are a class of proteins that interact with diverse prot ein substrates to assist in their folding, with a critical role during cell stress to prevent the appearance of folding intermediates that lead to mis folded or otherwise damaged molecules. Consequently, heat shock proteins as sist in the recovery from stress either by repairing damaged proteins (prot ein refolding) or by degrading them, thus restoring protein homeostasis and promoting cell survival. The events of cell stress and cell death are link ed, such that molecular chaperones induced in response to stress appear to function at key regulatory points in the control of apoptosis, On the basis of these observations-and on the role of molecular chaperones in the regul ation of steroid aporeceptors, kinases, caspases, and other protein remodel ing events involved in chromosome replication and changes in cell structure -it is not surprising that the heat shock response and molecular chaperones have been implicated in the control of cell growth. in this review, we add ress some of the molecular and cellular events initiated by cell stress-the interrelationships between stress signaling, cell death, and oncogenesis-a nd chaperones as potential targets for cancer diagnosis and treatment.