Date of Award
2011
Degree Type
Thesis
Degree Name
Master of Science
Program
Biochemistry
Supervisor
Dr. Fred Dick
Abstract
The E2F1 transcription factor transcribes the genes necessary for S phase progression and induces apoptosis when activated by DNA damage. Therefore, E2F1 has an interesting dual role, acting as a classical proto-oncogene or tumor suppressor depending on the cellular context. What remains unknown is the contribution of pRB regulation of E2F1 to E2F1-dependent apoptosis in response to DNA damage. I have studied the regulation of pRB and E2F1 interactions by DNA damage-responsive post- translational modifications in order to characterize the functional role of pRB/E2Fl complexes in response to genotoxic stress. I report that DNA damage directs the formation of distinctly modified pRB/E2Fl complexes. I characterize the post-translational modifications and functional role of two pRB/E2Fl complexes. Following DNA damage, acetylated E2F1 and pRB comprise a pRB/E2Fl complex that includes primarily hypophosphorylated pRB and CHK2 phosphorylated E2F1 forms a transcriptionally active, proapoptotic complex with hyperphosphorylated pRB that excludes other post- translational modifications.
Recommended Citation
Carnevale, Jasmyne, "INVESTIGATING THE ROLE OF POST-TRANSLATIONAL MODIFICATIONS OF THE RETINOBLASTOMA TUMOR SUPPRESSOR PROTEIN AND E2F1 TRANSCRIPTION FACTOR IN REGULATING APOPTOSIS FOLLOWING DNA DAMAGE" (2011). Digitized Theses. 3414.
https://ir.lib.uwo.ca/digitizedtheses/3414