Mutations in PEP4 locus of Saccharomyces cerevisiae block final step in maturation of two vacuolar hydrolases.

The biosynthesis of carboxypeptidase Y (EC 3.4.16.1) and proteinase A (EC 3.4.23.6) in yeast cells involves a series of posttranslational events, the last of which is dependent upon a function supplied by the PEP4 gene. Because pep4 mutations result in a 90-95% reduction in the levels of activity of at least three additional vacuolar hydrolases, it is likely that these, and perhaps all, yeast vacuolar hydrolases are synthesized as inactive precursors, which mature by a common mechanism that depends upon a function supplied by the PEP4 gene. The pep4 mutation shows an apparent gene dosage effect on levels of activity of proteinases A and B but not on the level of activity of carboxypeptidase Y. This effect appears to come about because the maturation machinery is capable of discriminating among these hydrolase precursors.