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Structural and Functional Evolution of Human Heat Shock Transcription Factors

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Date
2015
Author
Jaeger, Alex M.
Advisor
Thiele, Dennis J
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Abstract

Proteotoxic stress is implicated in numerous human diseases including neurodegeneration, cancer, and diabetes. Unfortunately, our mechanistic understanding of the cellular response to proteotoxic stress is limited. A critical feature of the cellular stress response is the activation of Heat Shock Transcription Factors (HSFs) that regulate the expression of numerous genes involved in protein folding, protein degradation, and cellular survival. The studies presented here utilize a diverse array of techniques including yeast genetics, recombinant protein expression and purification, biochemical analysis of protein-DNA interactions, x-ray crystallography, in vitro post-translational modification, and mammalian cell culture to illuminate novel aspects of HSF biology. Critical findings include understanding key principles of HSF-DNA interactions, identification of a novel negative regulator of HSF activity, and identification of structural features of HSF paralogs that enable precise combinatorial regulation. These unique insights lay the foundation for a greater understanding of HSF in specific cellular contexts and disease states.

Type
Dissertation
Department
Pharmacology
Subject
Biochemistry
Biology
Pharmacology
Cell Stress
Heat Shock Factor
Protein Chaperones
Protein-DNA Interaction
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https://hdl.handle.net/10161/10517
Citation
Jaeger, Alex M. (2015). Structural and Functional Evolution of Human Heat Shock Transcription Factors. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/10517.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

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