THE SACCHAROMYCES SHP1 GENE, WHICH ENCODES A REGULATOR OF PHOSPHOPROTEIN PHOSPHATASE-1 WITH DIFFERENTIAL-EFFECTS ON GLYCOGEN-METABOLISM, MEIOTIC DIFFERENTIATION, AND MITOTIC CELL-CYCLE PROGRESSION

The phosphoprotein phosphatase 1 (PP1) catalytic subunit encoded by th e Saccharomyces GLC7 gene is involved in control of glycogen metabolis m, meiosis, translation, chromosome segregation, cell polarity, and G( 2)/M cell cycle progression. It is also lethal when overproduced. We h ave isolated strains which are resistant to Glc7p overproduction letha lity as a result of mutations in the SHP1 (suppressor of high-copy PP1 ) gene, which was previously encountered in a genomic sequencing proje ct as an open reading frame whose interruption totally blocked sporula tion and slightly slowed cell proliferation. These phenotypes also cha racterized our shp1 mutations, as did deficient glycogen accumulation. Lysates from the shp1 mutants were deficient in PP1 catalytic activit y but exhibited no obvious abnormalities in the steady-state level or subcellular localization pattern of a catalytically active Glc7p-hemag glutinin fusion polypeptide. The lower level of PP1 activity in shp1 c ells permitted substitution of a galactose-induced GAL10-GLC7 fusion f or GLC7; depletion of Glc7p from these cells by growth in glucose medi um resulted in G(2)/M arrest as previously observed for glc(7)(cs) all ele but with depletion arrest occurring most frequently at a later sta ge of mitosis. The higher requirement of glycogen accumulation and spo rulation for PP1 activity would permit their regulation via Glc7p acti vity, independent of its requirement for mitosis.