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FEBS Open Bio. 2018 Aug 1;8(9):1486-1496. doi: 10.1002/2211-5463.12485. eCollection 2018 Sep.

A stable association with PME-1 may be dispensable for PP2A demethylation - implications for the detection of PP2A methylation and immunoprecipitation.

Author information

1
Laboratory of Veterinary Pharmacology Joint Faculty of Veterinary Medicine Yamaguchi University Japan.
2
Priority Organization for Innovation and Excellence Kumamoto University Japan.
3
Department of Food Science and Technology National Fisheries University Shimonoseki Japan.
4
Laboratory of Veterinary Pharmacology Faculty of Agriculture Tokyo University of Agriculture and Technology Fuchu Japan.

Abstract

Reversible methyl-esterification (methylation) of Leu309 in the protein phosphatase 2A catalytic subunit (PP2Ac) is essential for proper biogenesis of the PP2A holoenzyme. Accumulating evidence links PP2Ac methylation to diseases, including cancer and neurodegenerative disorders. Protein phosphatase methyl-esterase (PME-1) specifically catalyzes PP2Ac demethylation. We demonstrate that PP2Ac is demethylated in cell extracts even at 0 °C unless prevented by a PME-1 methyl-esterase inhibitor. This promotes dissociation of PP2A heterotrimers with B55 or PR72 subunits, but not those with B56 subunits. These results reveal differential sensitivity of ABC heterotrimers to methylation status of the C subunit. Our study advocates caution when interpreting earlier findings, offers an effective protocol for preserving PP2A complexes, and reveals key distinctions between B subunits and their interactions with the AC core dimer of PP2A.

KEYWORDS:

demethylation; protein methylation; protein phosphatase 2A; protein phosphatase methyl‐esterase

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