Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Biochemistry
Supervisor
Dr. Fred Dick
Second Advisor
Dr. Eric Ball
Third Advisor
Dr. Gabriel DiMattia
Abstract
The Retinoblastoma tumour suppressor protein (pRB) functions to negatively regulate cell proliferation by inhibiting E2F transcription factor activity. Additionally, an essential function of pRB in the inhibition of apoptosis induced by E2F1 has been documented. The mechanism dictating the ability of pRB to differentially regulate these opposing E2F functions has remained largely elusive. In this thesis I describe the generation of an RB mutant protein that is defective in mediating an E2Fl-t Specific’ binding interaction. This protein retains the ability to inhibit both E2F-mediated transcription and cell cycle entry but is defective in apoptotic regulation, these functions are in contrast to those of the previously described E2F-‘General’ pRB binding mutant. Interestingly, pRB-E2F ‘General’ and ‘Specific’ complexes exhibit different DNA binding specificities. Furthermore, the E2Fl-‘Specific’ domain is uniquely conserved among pRB homologues in higher eukaryotes, highlighting the importance of this apoptotic regulatory domain to pRB function.
Recommended Citation
Julian, Lisa Marie, "An E2Fl-‘Specific’ Binding Domain Within pRB is Required for Regulation of E2F1-Induced Apoptosis" (2006). Digitized Theses. 4682.
https://ir.lib.uwo.ca/digitizedtheses/4682