Abstract
The phosphoprotein phosphatase 2A (PP2A) catalytic subunit contains a methyl ester on its C-terminus, which in mammalian cells is added by a specific carboxyl methyltransferase and removed by a specific carboxyl methylesterase. We have identified genes in yeast that show significant homology to human carboxyl methyltransferase and methylesterase. Extracts of wild-type yeast cells contain carboxyl methyltransferase activity, while extracts of strains deleted for one of the methyltransferase genes, PPM1, lack all activity. Mutation of PPM1 partially disrupts the PP2A holoenzyme in vivo and ppm1 mutations exhibit synthetic lethality with mutations in genes encoding the B or B' regulatory subunit. Inactivation of PPM1 or overexpression of PPE1, the yeast gene homologous to bovine methylesterase, yields phenotypes similar to those observed after inactivation of either regulatory subunit. These phenotypes can be reversed by overexpression of the B regulatory subunit. These results demonstrate that Ppm1 is the sole PP2A methyltransferase in yeast and that its activity is required for the integrity of the PP2A holoenzyme.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cattle
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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DNA, Complementary / genetics
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DNA, Complementary / isolation & purification
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Drug Resistance, Microbial
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Gene Expression
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Genes, Fungal
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Humans
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Methylation
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Molecular Sequence Data
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Mutation
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Phenotype
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Phosphoprotein Phosphatases / chemistry*
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism*
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Protein Methyltransferases / chemistry
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Protein Methyltransferases / genetics
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Protein Methyltransferases / metabolism
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Protein Phosphatase 2
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Protein Subunits
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins*
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Schizosaccharomyces pombe Proteins*
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Sequence Homology, Amino Acid
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Sirolimus / pharmacology
Substances
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CDC55 protein, S cerevisiae
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Cell Cycle Proteins
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DNA, Complementary
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Fungal Proteins
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Protein Subunits
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Saccharomyces cerevisiae Proteins
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Schizosaccharomyces pombe Proteins
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Protein Methyltransferases
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protein-S-isoprenylcysteine O-methyltransferase
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ppe1 protein, S pombe
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Phosphoprotein Phosphatases
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Protein Phosphatase 2
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Sirolimus