The overall objective of this project is to understand the role of E2F transcription factor in regulation of cell proliferation and how a loss of this regulation can lead to oncogenesis. Indications that the cellular transcription factor E2F plays a role in cell proliferation control was obtained from recent analyses which demonstrated a physical interaction between the tumor suppressor protein Rb and E2F. Further, the loss of Rb function is closely associated with a loss of the Rb-E2F interaction, suggesting that E2F is a functionally relevant target for Rb. Additional proteins involved in cell cycle regulation like p 107, cyclins A and E, and the kinase cdk2 are also found to be associated with E2F, indicating that E2F could be playing a major role in regulating cell proliferation. This project aims at studying the role of E2F in tumorigenesis, differentiation and cell cycle regulation. It will be assessed whether there is correlation between the loss of the Rb-E2F interaction and the generation of a wide variety of human tumors. In addition, the possibility that a mutation of E2F can lead to oncogenesis will be examined. To further understand the mechanism of E2F action, additional proteins that interact with E2F will be identified and cloned. Experiments will also be conducted on the role of E2F and associated proteins in the differentiation process of cells. Finally, attempts will be made to identify the cellular promoters that are targeted by E2F an E2F associated proteins.
Showing the most recent 10 out of 29 publications
