2005 Ohio Student Research Forum

Abstract

Role of the Rb/E2F2 Pathway in Intestine Development
MiLinda Nimmo
Ohio State University, Department of Biology and Chemistry
Mentor: Dr. Gustave Leone

The protein product of Rb, retinoblastoma, is a complex regulator of gene transcription that controls the cell cycle, apoptosis, and differentiation. In its active hypo-phosphorylated form, Rb can suppress entrance into the S phase of the cell cycle by inhibiting E2F-dependent transcription. It is achieved by the binding of Rb to E2Fs, which results in blocking E2Fs’ abilities to activate transcription. In biological systems, Rb is inactivated by phosphorylation. The phosphorylated Rb is dissociated from E2Fs, resulting in an up-regulation of E2F activities that in turn activate genes required for DNA synthesis and cell cycle entry.

It is now clear that E2F transcription factors are key regulators of cell cycle progression. The E2F family can be split into four sub-categories based on their main purpose and mechanism by which the purpose is achieved. Specifically, E2F2 is classified as an activating group member because it is required for transactivation of target genes involved in the G1/S transition. Consequently, E2F2 is needed for correct progression through the cell cycle.

Using the mouse model, Rb has been conditionally knocked out in whole embryos by using Mox2Cre. Preliminary data shows that there is an up regulation of E2F2 and E2F3a in the intestine. This is coupled with intestinal hyperplasia. Based on these results, it is believed that over expression of E2Fs could play a significant role in tumorigenesis. As a result, Rb and E2F2 double deletion mice have been generated to determine if decreased levels of E2F2 can rescue the Rb knock out phenotype.