Date of Graduation


Document Type


Degree Type



School of Medicine


Microbiology, Immunology, and Cell Biology

Committee Chair

Laura Gibson


Caspases are proteolytic enzymes involved in committing apoptosis, but through the studies of knockout phenotypes in mice and Drosophila , it has been speculated that caspases might possess additional non-apoptotic functions.;We have found non-apoptotic functions for caspase-8 in both normal and tumor cell lines. Specifically, we found that caspase-8 promotes cell migration, adhesion, and Rac activation. Subsequently, we also found that caspase-8 interacts with the p85 subunit of PI3K. Accompanying stimulation of motility with epidermal growth factor the phosphorylation of caspase-8 on tyrosine-380 is induced and this phosphorylation allows for p85 interaction, cell migration, adhesion, and Rac activation. Caspase-8 also promoted EGF-induced Erk activation, stimulating cell migration.;Non-apoptotic functions also exist for caspase-2. We demonstrate that caspase-2 promotes cell-matrix adhesion, focal contact formation and FAK phosphorylation. Caspase 2 also mediates stress fiber dissolution in response to protein kinase-C activation. Insights into the mechanism whereby caspase 2 influences cytoskeletal processes with emphasis on Rho/ROCK/LIMK/cofilin and Rho/ROCK/MLC pathways are discussed.;These findings demonstrate a non-apoptotic function of a caspase involving signaling protein interactions rather than proteolysis. This is also the first report that caspase-2 and caspase-8 may mediate cytoskeletal functions independent of cell death.