It is well established that the Rb and E2F protein family members are important regulators of (GI to S phase progression and apoptosis. Moreover, mutations in the """"""""Rb/E2F pathway"""""""" are important contributors to human neoplasia. Therefore, it is important to understand how Rb and E2F proteins regulate both cell cycle and death. However, studies of mammalian Rb and E2F function have been hindered by the lack of a suitable genetic system and by the large family of Rb and E2F genes. Studies of Rb and E2F function in Drosophila are ideal since these gene families are smaller and the development and genetic manipulation of the organism is well understood. Therefore, the proposed research aims to identify important regulators of Rbf and dE2F activity in vivo. In the first approach, both novel preexisting and prospective dE2F- and Rbf-dependent phenotypes will characterized in vivo. In the second approach, mutations in genes which modify these phenotypes will be isolated using a genetic screening strategy. This approach has the ability to identify new proteins involved in Rbf and dE2F function that have not been identified in mammalian systems. Identification of novel regulators of both Rbf and dE2F function will facilitate our understanding of the function of these genes in vivo and ultimately during development and tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA088474-02
Application #
6514766
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Lohrey, Nancy
Project Start
2002-07-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$50,116
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Morris, Erick J; Michaud, William A; Ji, Jun-Yuan et al. (2006) Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet 2:e196
Frolov, Maxim V; Stevaux, Olivier; Moon, Nam-Sung et al. (2003) G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression. Genes Dev 17:723-8
Stevaux, Olivier; Dimova, Dessislava; Frolov, Maxim V et al. (2002) Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2. EMBO J 21:4927-37