A Stable Association with PME-1 May Be Dispensable for PP2A Demethylation - Implications for the Detection of PP2A Methylation and Immunoprecipitation

Overview

Journal FEBS Open Bio

Specialty Biology

Date 2018 Sep 7

PMID 30186749

Citations 11

Authors

Ryotaro Yabe

Shunya Tsuji

Satoru Mochida

Tsuyoshi Ikehara

Tatsuya Usui

Takashi Ohama

Koichi Sato

Affiliations

Soon will be listed here.

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.

Citing Articles

PME-1 sensitizes glioblastoma cells to oxidative stress-induced cell death by attenuating PP2A-B55α-mediated inactivation of MAPKAPK2-RIPK1 signaling.

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Haanen 3rd T, OConnor C, Narla G J Biol Chem. 2022; 298(12):102656.

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Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition.

Li Y, Balakrishnan V, Rowse M, Wu C, Bravos A, Yadav V Elife. 2022; 11.

PMID: 35924897 PMC: 9398451. DOI: 10.7554/eLife.79736.

Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation.

Lyons S, Greiner E, Cressey L, Adamo M, Kettenbach A Sci Rep. 2021; 11(1):23031.

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A phosphatase-centric mechanism drives stress signaling response.

Hollenstein D, Gerecova G, Romanov N, Ferrari J, Veis J, Janschitz M EMBO Rep. 2021; 22(11):e52476.

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