The Saccharomyces cerevisiae homologue YPA1 of the mammalian phosphotyrosyl phosphatase activator of protein phosphatase 2A controls progression through the G1 phase of the yeast cell cycle

The Saccharomyces cerevisiae gene YPA1 encodes a protein homologous to the phosphotyrosyl phosphatase activator, PTPA, of the mammalian protein phosph atase type 2A (PP2A). In order to examine the biological role of PTPA, we d isrupted YPA1 and characterised the phenotype of the ypa1 Delta mutant. Com parison of the growth rate of the wild-type strain and the ypa1 Delta mutan t on glucose-rich medium after nutrient depletion showed that the ypa1 Delt a mutant traversed the lag period more rapidly. This accelerated progressio n through "Start" was also observed after release from alpha-factor-induced G1 arrest as evidenced by a higher number of budding cells, a faster incre ase in CLN2 mRNA expression and a more rapid reactivation of Cdc28 kinase a ctivity. This phenotype was specific for deletion of YPA1 since it was not observed when YPA2, the second PTPA gene in budding yeast was deleted. Rein troduction of YPA1 or the human PTPA cDNA in the ypa1 Delta mutant suppress ed this phenotype as opposed to overexpression of YPA2. Disruption of both YPA genes is lethal, since sporulation of heterozygous diploids resulted in at most three viable spores, none of them with a ypa1 Delta ypa2 Delta gen otype. This observation indicates that YPA1 and YPA2 share some essential f unctions. We compared the ypa1 Delta mutant phenotype with a PP2A double de letion mutant and a PP2A temperature-sensitive mutant. The PP2A-deficient y east strain also showed accelerated progression through the G1 phase. In ad dition, both PP2A and ypa1 Delta mutants show similar aberrant bud morpholo gy. This would support the notion that YPA1 may act as a positive regulator of PP2A in vivo. (C) 2000 Academic Press.