Phosphate starvaton induces the transcription of several genes involved in phosphate metabolism in the budding yeast Saccharomyces cerevisiae. The signal transduction pathway that mediates this response consists of components that resemble those used to regulate the eukaryotic cell cycle; these include a cyclin-dependent kinase or CDK (Pho85), a cyclin (Pho80) and a CDK inhibitor (Pho81). When yeast cells are starved for phosphate, Pho81p inhibits the activity of the Pho80-Pho85 complex, so that the transcription factor Pho4p is inactivated, and thus the genes involved in phophsphate metabolism are turned off. A region of Pho81 is consists of six ankyrin repeats, and this domain is similar to the mammalian CDK inhibitor p16INK4 and it is sufficient for inhibition of Pho80-Pho85 CDK activity in vitro. I am focusing on studies of the regulation and molecular mechanism of Pho81p. I am investigating questions such as whether Pho81 protein changes its conformation when yeast cells are in phosphate rich or phosphate depleted media, which domain is responsible for the regulation of its activity and which domain interacts physically with the CDK complex. The Computer Graphics Laboratory provides invaluable help to my research. I use the facilities and software to model the possible interaction between Pho81 and Pho80- Pho85 complex. Together with experimental data, I am confident that the molecular mechanism of the CDK inhibitor Pho81p will be sorted out in the near future.
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