The yeast Ser/Thr phosphatases Sit4 and Ppz1 play opposite roles in regulation of the cell cycle

Yeast cells overexpressing the Ser/Thr protein phosphatase Ppz1 display a s low-growth phenotype. These cells recover slowly from alpha-factor or nutri ent depletion-induced G(1) arrest, showing a considerable delay in bud emer gence as well as in the expression of the G(1) cyclins Cln2 and Clb5. There fore, an excess of the Ppz1 phosphatase interferes with the normal transiti on from G(1) to S phase. The growth defect is rescued by overexpression of the HAL3/SIS2 gene, encoding a negative regulator of Ppz1. High-copy-number expression of HAL3/SIS2 has been reported to improve cell growth and to in crease expression of G(1) cyclins in sit4 phosphatase mutants. We show here that the described effects of HAL3/SIS2 on sit4 mutants are fully mediated by the Ppz1 phosphatase. The growth defect caused by overexpression of PPZ 1 is intensified in strains with low G(1) cyclin levels (such as bck2 Delta or cln3 Delta mutants), whereas mutation of PPZ1 rescues the synthetic let hal phenotype of sit4 cln3 mutants. These results reveal a role for Ppz1 as a regulatory component of the yeast cell cycle, reinforce the notion that Hal3/Sis2 serves as a negative modulator of the biological functions of Ppz 1, and indicate that the Sit4 and Ppz1 Ser/Thr phosphatases play opposite r oles in control of the G(1)/S transition.