CATABOLITE INACTIVATION OF FRUCTOSE-1,6-BISPHOSPHATASE IN YEAST IS MEDIATED BY THE PROTEASOME

Fructose-1,6-bisphosphatase, a key enzyme in gluconeogenesis, undergoe s catabolite inactivation when glucose is added to gluconeogenetically active cells of the yeast Saccharomyces cerevisiae. Phosphorylation o f the enzyme is followed by rapid degradation. To elucidate the cellul ar proteolytic system involved in catabolite-triggered degradation of fructose-1,6-bisphosphatase this event was followed in different prote ase-deficient yeast mutants. In a mutant defective in the proteolytic function of the vacuole the degradation rate of the enzyme is not dimi nished. In contrast mutants defective in the proteolytic activity of t he proteasome exhibit a strongly reduced glucose-induced degradation o f fructose-1,6-bisphosphatase as compared to their isogenic wild-type counterparts. Our studies suggest that catabolite inactivation of fruc tose-1,6-bisphosphatase occurs in the cytosol, the degradation event b eing mediated by the proteasome. An explanation is presented which tri es to resolve the formerly conflicting results, which suggested glucos e-triggered uptake of fructose-1,6-bisphosphatase into the vacuole fol lowed by vacuolar proteolysis.