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PP2A-B55: substrates and regulators in the control of cellular functions

Oncogene volume 41, pages 1–14 (2022)Cite this article

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Abstract

PP2A is a major serine/threonine phosphatase class involved in the regulation of cell signaling through the removal of protein phosphorylation. This class of phosphatases is comprised of different heterotrimeric complexes displaying distinct substrate specificities. The present review will focus on one specific heterocomplex, the phosphatase PP2A-B55. Herein, we will report the direct substrates of this phosphatase identified to date, and its impact on different cell signaling cascades. We will additionally describe its negative regulation by its inhibitors Arpp19 and ENSA and their upstream kinase Greatwall. Finally, we will describe the essential molecular features defining PP2A-B55 substrate specificity that confer the correct temporal pattern of substrate dephosphorylation. The main objective of this review is to provide the reader with a unique source compiling all the knowledge of this particular holoenzyme that has evolved as a key enzyme for cell homeostasis and cancer development.

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Fig. 1: Crystal structure of PP2A holoenzymes and inhibitors.
Fig. 2: Schematic overview of the role of PP2A-B55 in the control of autophagy.
Fig. 3: Role of PP2A-B55 in metabolism.
Fig. 4: Schematic representation of the signaling pathways controlled by PP2A-B55 in S, G2, and M phases of the cell cycle.
Fig. 5: Molecular mechanisms controlling PP2A-B55 inhibitory activity of Arpp19.

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Funding

This work was supported by the Agence National de la Recherche (KiPARPP, ANR-18-CE13-0013 and REPLIGREAT, ANR-18-CE13-0018-01), La Ligue Nationale Contre le Cancer (Equipe Labellisée, EL2019 CASTRO), the Fondation ARC (PJA 20181207931), and the LABEX EpiGenMed (ANR-10-LABEX-12-01). PA is a Fondation pour la Recherche Medicale (FRM) fellow. SA and SR are LABEX EpiGenMed fellows.

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  1. Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), CNRS UMR 5237, Université de Montpellier, 1919 Route de Mende, Montpellier Cedex 5, Montpellier, 34293, France

    Priya Amin, Sushil Awal, Suzanne Vigneron, Sylvain Roque, Francisca Mechali, Jean Claude Labbé, Thierry Lorca & Anna Castro

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  1. Priya Amin
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  2. Sushil Awal
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  3. Suzanne Vigneron
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  4. Sylvain Roque
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  7. Thierry Lorca
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Contributions

PA and SA contributed to the writing of PP2A-B55/Hippo-Yap and PP2A-/B55/cell metabolism sections. SV, FM, SR, JCL, and TL contributed to the writing of the Arpp19/mitotic control. AC performed the rest and coordinated the different sections.

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Correspondence to Thierry Lorca or Anna Castro.

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The authors declare no competing interests.

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Amin, P., Awal, S., Vigneron, S. et al. PP2A-B55: substrates and regulators in the control of cellular functions. Oncogene 41, 1–14 (2022). https://doi.org/10.1038/s41388-021-02068-x

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  • DOI: https://doi.org/10.1038/s41388-021-02068-x

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