Mutation of the C-terminal leucine residue of PP2Ac inhibits PR55/B subunit binding and confers supersensitivity to microtubule destabilization in Saccharomyces cerevisiae
| Autor: | D. R. H. Evans, B. A. Hemmings |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Protein subunit Saccharomyces cerevisiae Cell Cycle Proteins In Vitro Techniques Microtubules Leucine Microtubule Phosphoprotein Phosphatases Genetics Humans Protein Phosphatase 2 Molecular Biology Mitosis Alanine biology Nocodazole General Medicine Protein phosphatase 2 biology.organism_classification Yeast Protein Subunits Biochemistry Mutation Benomyl Cell Division |
| Zdroj: | Molecular Genetics and Genomics. 264:425-432 |
| ISSN: | 1617-4623 1617-4615 |
| Popis: | Protein phosphatase 2A is ubiquitous among eukaryotes and exists as a family of holoenzymes in which the catalytic subunit. PP2Ac, binds a variety of regulatory subunits. Using the yeast Saccharomyces cerevisia, we have investigated the role of the phylogenetically invariant C-terminal leucine residue of PP2Ac, which, in mammalian cells, undergoes reversible methylation and modulates binding of the PR55/B subunit. In S. cerevisiae, the C-terminal Leu-377 residue of Pph22p (equivalent to human PP2Ac Leu-309) was dispensable for cell growth under optimum conditions and its removal, or substitution by alanine, did not inhibit PP2A activity in vitro. However, Leu-377 is required for binding of the yeast PR55/B subunit, Cdc55p, by Pph22p, though apparently not for the binding of Rts1p, the yeast PR61/B' subunit. Furthermore, mutation of this leucine enhanced the sensitivity of cells to microtubule destabilization, a defect characteristic of cdc55delta mutant cells, which are impaired for spindle checkpoint function. These results demonstrate that the regulation of PP2A, mediated by PR55/B binding to the highly conserved PP2Ac C-terminus, is critical for cell viability under conditions of microtubule damage and support a role for PP2A in exit from mitosis. |
| Databáze: | OpenAIRE |
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