HFP ACTIVATES PROTEOLYSIS OF POSITIVE CELL CYCLE REGULATORS TO INHIBIT CELL CYCLE PROGRESSION IN DROSOPHILA [ 2005 - 2007 ]

Research Grant

Researchers: Dr Leonie Quinn (Principal investigator)

Brief description Cell proliferation is essential for animal development and tissue regeneration. In order to proliferate, cells must double their DNA contents and segregate their chromosomes precisely into daughter cells. Collectively this series of events is referred to as the Cell Cycle. The cell cycle must be carefully regulated since inappropriate proliferation can cause developmental abnormalities and tumour formation in multicellular animals. Proliferation is regulated by a balanced set of interactions between two group of proteins, cell cycle activators and cell cycle inhibitors. Aberrations in cell cycle inhibitor proteins will cause excessive cell proliferation, the first step in the multi-step process of tumour development. It is important to understand the processes that normally inhibit cell proliferation, since cells undergoing more rapid cell cycles are much more likely to develop further errors in their genetic material and progress to later stage invasive tumours. This proposal focuses on a protein (FIR-Hfp) that we have shown to inhibit cell cycle progression in the vinegar fly (Drosophila Melanogaster), which is an excellent model organism for studying developmentally regulated cell proliferation. Furthermore, most cell cycle regulators are conserved in evolution, so the knowledge derived from these studies can assist with our understanding of how complex pathways might coordinate proliferation mammals. FIR-Hfp negatively regulates cell proliferation by down-regulating cycle activator proteins (dMyc and Stg). At present the mechanism for the inhibitory affect on these activators is not understood, but preliminary data suggests that FIR-Hfp might be involved in causing Stg and the dMyc activator protein (Hay) to be targeted for destruction. The aim of this project is to elucidate the mechanism by which Hfp regulates the activity of these potentially ocogenic factors, and thus gain a better understanding of the preliminary stages of tumour progression.

Funding Amount $AUD 438,750.00

Funding Scheme NHMRC Project Grants

Notes New Investigator Grant