Analysis of mechanisms affecting dE2F1 stability and protein levels in the fruitfly Drosophila melanogaster

• Applicant: Dr. Michael Korenjak
• Subject Area: Cell Biology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 56850196

E2F transcription factors are critical regulators of the eukaryotic cell cycle. In the past, studies of E2F have concentrated on the regulation of gene expression mediated by E2F and the synthesis of E2F. On the other hand, dramatic changes in E2F protein levels can be observed in vivo, that do not seem to result from changes in transcription. The mechanism(s) responsible for this remain unknown, but it is very likely that timely elimination by the ubiquitin-proteasome system plays an essential role. Like their mammalian counterparts, Drosophila melanogaster E2F proteins (dE2Fs) play a critical role in cell cycle regulation. The lower level of complexity of the Drosophila genome, however, facilitates the analysis of these factors in the fly. In the course of the proposed project, I will perform an unbiased genome-wide screen for modifiers of dE2F1 stability. The results from this screen will be validated in vivo in the context of animal development. As a complementary approach, I will analyze a set of modifiers of a dE2F1 dsRNA-induced cell proliferation phenotype, which were identified in a genetic screen in the host laboratory, and, interestingly, include components of the ubiquitin-proteasome system. Finally, I will analyze the mechanisms responsible for the tight regulation of dE2F1 protein levels that can be observed in specific situations during fly development. The knowledge gained from these studies will improve our understanding of crucial biological processes, such as proliferation, differentiation and apoptosis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Nicholas Dyson