Signal Transduction Mechanism of The Heat Shock Response in Cell Aging

Project Details


The heat shock response, defined as the rapid induction of heat shock proteins (HSPs), was first described in 1962 by Ritossa in Drosophila. It has since been shown that the response is ubiquitous in all living organisms, that it can be elicited by a wide range of physiological and noxious stimuli, and that the genes and proteins of HSPs are highly conserved through evolution. These features underscore the importance of HSPs in biology. This laboratory has shown that the heat shock response is attenuated in senescent human diploid fibroblasts. Experiments are proposed to study the signal transduction mechanism of the heat shock response and the regulation of this mechanism in cell aging. Specifically, experiments are proposed to evaluate if cAMP and cAMP-dependent protein kinase may participate in the regulation of heat shock gene expression, and if so, whether this regulation is through the basal or the inducible promoter element. The approaches to be used include: analysis of the effects of expression vectors of cAMP- dependent protein kinase and the protein kinase inhibitor on the basal and heat induced expression of the hsp 70 promoter driven reporter gene; and determining the effects of cAMP-elevating agents on the expression of the endogenous and transfected hsp 70 gene. The wealth of knowledge of the molecular organization of the heat shock genes, the age-dependent attenuation of this induction, and the acknowledged importance of cAMP and cAMP-dependent protein kinase as a biological control mechanism are features that make this system particularly useful in analysis of signal transduction and gene expression. The long-range goal of this research program is to gain a better understanding of the regulation and function of heat shock genes.

Effective start/end date9/1/918/31/93


  • National Science Foundation: $50,000.00


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