Journal Article

Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death

Caroline Jolly and Richard I. Morimoto

in JNCI: Journal of the National Cancer Institute

Volume 92, issue 19, pages 1564-1572
Published in print October 2000 | ISSN: 0027-8874
Published online October 2000 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/92.19.1564
Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death

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Exposure of cells to conditions of environmental stress—including heat shock, oxidative stress, heavy metals, or pathologic conditions, such as ischemia and reperfusion, inflammation, tissue damage, infection, and mutant proteins associated with genetic diseases—results in the inducible expression of heat shock proteins that function as molecular chaperones or proteases. Molecular chaperones are a class of proteins that interact with diverse protein substrates to assist in their folding, with a critical role during cell stress to prevent the appearance of folding intermediates that lead to misfolded or otherwise damaged molecules. Consequently, heat shock proteins assist in the recovery from stress either by repairing damaged proteins (protein refolding) or by degrading them, thus restoring protein homeostasis and promoting cell survival. The events of cell stress and cell death are linked, 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 regulation of steroid aporeceptors, kinases, caspases, and other protein remodeling 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 address some of the molecular and cellular events initiated by cell stress—the interrelationships between stress signaling, cell death, and oncogenesis—and chaperones as potential targets for cancer diagnosis and treatment.

Journal Article.  8621 words.  Illustrated.

Subjects: Medical Oncology

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