Abstract for presentation at 11th International Congress of Human Genetics

The aim of this project is to investigate the role of genes involved in the response to nutrient depletion using as a model extracellular protease production in the filamentous fungus, Aspergillus nidulans. In A. nidulans, extracellular proteases are produced in response to carbon-, nitrogen- or sulfur-nutrient limitation. We have shown that two atypical hexokinases (HxkC and HxkD) are involved in the regulation of extracellular protease production in A. nidulans. Hexokinases catalyse the first step in glucose metabolism and play a role in glucose sensing in mammals, plants and fungi. Most, but not all, of the highly conserved residues within the ATP- and sugar-binding domains of other eukaryotic hexokinases are present in HxkC and HxkD. However, these atypical hexokinases have putative nuclear localization signals and additional sequences that may provide them with new functions. We have shown that HxkD is a nuclear protein and purified recombinant HxkD lacks sugar-phosphorylating activity indicating that HxkC and HxkD may be solely regulatory in function We have identified a third protein (XprG) that, like XprF and HxkC, is involved in the response to starvation. The xprG gene product belongs to a newly defined class of DNA-binding proteins which includes a transcriptional activator required for progression through meiosis in yeast and a human protein shown to be highly expressed in metastatic tumour cells. We have shown that xprG null mutants do not produce extracellular proteases in response to carbon, nitrogen or sulphur limitation. In addition, they are defective in the production of an acid phosphatase in response to phosphate limitation. Thus, it seems likely that XprG mediates the response to nutrient limitation of any type. However, different proteins (e.g. XprF and HxkC) may interact with XprG to activate the response to carbon, sulphur, nitrogen, or phosphate depletion.