A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation
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...
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| Format: | Article |
| Language: | English |
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Wiley
2018-09-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12485 |
| _version_ | 1797871021833846784 |
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| author | Ryotaro Yabe Shunya Tsuji Satoru Mochida Tsuyoshi Ikehara Tatsuya Usui Takashi Ohama Koichi Sato |
| author_facet | Ryotaro Yabe Shunya Tsuji Satoru Mochida Tsuyoshi Ikehara Tatsuya Usui Takashi Ohama Koichi Sato |
| author_sort | Ryotaro Yabe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T00:37:43Z |
| format | Article |
| id | doaj.art-aa84b8c027ea43db99e5813fce983440 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-10T00:37:43Z |
| publishDate | 2018-09-01 |
| publisher | Wiley |
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| spelling | doaj.art-aa84b8c027ea43db99e5813fce9834402023-03-14T13:05:47ZengWileyFEBS Open Bio2211-54632018-09-01891486149610.1002/2211-5463.12485A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitationRyotaro Yabe0Shunya Tsuji1Satoru Mochida2Tsuyoshi Ikehara3Tatsuya Usui4Takashi Ohama5Koichi Sato6Laboratory of Veterinary Pharmacology Joint Faculty of Veterinary Medicine Yamaguchi University JapanLaboratory of Veterinary Pharmacology Joint Faculty of Veterinary Medicine Yamaguchi University JapanPriority Organization for Innovation and Excellence Kumamoto University JapanDepartment of Food Science and Technology National Fisheries University Shimonoseki JapanLaboratory of Veterinary Pharmacology Faculty of Agriculture Tokyo University of Agriculture and Technology Fuchu JapanLaboratory of Veterinary Pharmacology Joint Faculty of Veterinary Medicine Yamaguchi University JapanLaboratory of Veterinary Pharmacology Joint Faculty of Veterinary Medicine Yamaguchi University JapanReversible 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.https://doi.org/10.1002/2211-5463.12485demethylationprotein methylationprotein phosphatase 2Aprotein phosphatase methyl‐esterase |
| spellingShingle | Ryotaro Yabe Shunya Tsuji Satoru Mochida Tsuyoshi Ikehara Tatsuya Usui Takashi Ohama Koichi Sato A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation FEBS Open Bio demethylation protein methylation protein phosphatase 2A protein phosphatase methyl‐esterase |
| title | A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation |
| title_full | A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation |
| title_fullStr | A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation |
| title_full_unstemmed | A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation |
| title_short | A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation |
| title_sort | stable association with pme 1 may be dispensable for pp2a demethylation implications for the detection of pp2a methylation and immunoprecipitation |
| topic | demethylation protein methylation protein phosphatase 2A protein phosphatase methyl‐esterase |
| url | https://doi.org/10.1002/2211-5463.12485 |
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