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Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann Jan 2013

Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann

Electronic Thesis and Dissertation Repository

The longevity associated protein p66Shc has been suggested to regulate organismal lifespan through initiation of apoptotic pathways. Following stress-induced translocation into the mitochondria, p66Shc promotes increased reactive oxygen species (ROS) production and triggers poorly defined downstream signaling events that lead to decreased cell viability. Protein disulfide bonding has recently emerged as aROSdependent post-translational modification that regulates protein function and signaling processes. Using the mouse hippocampal HT-22 cell line, I sought to determine the changes in the disulfide proteome associated with p66Shc mediatedROSproduction. Through Redox 2D-SDSPAGEanalysis of mitochondrial and cytosolic extracts, redox sensitive proteins altered by p66Shc mediatedROSformation were identified. Of ...


Regulation And Dynamic Behavior Of The Heat Shock Transcription Factor Hsf-1 In C. Elegans, Elizabeth A. Morton Jan 2013

Regulation And Dynamic Behavior Of The Heat Shock Transcription Factor Hsf-1 In C. Elegans, Elizabeth A. Morton

Publicly Accessible Penn Dissertations

Eukaryotic cells respond to heat stress by activating the transcription factor HSF1. In addition to its role in stress response, HSF1 also functions in protein homeostasis, aging, innate immunity, and cancer. Despite prominent HSF1 involvement in processes pertinent to human health and disease, there are still gaps in our understanding of HSF1. For example, controversy exists regarding the localization of HSF1, the identity of HSF1 regulators, and the function and conservation of heat-induced HSF1 stress granules. Many of the physiological roles for HSF1 have been defined using the model organism Caenorhabditis elegans, yet little is known about how the molecular ...