FAM122A, a New Endogenous Inhibitor of Protein Phosphatase 2A

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Sep 3

PMID 27588481

Citations 15

Authors

Li Fan

Man-Hua Liu

Meng Guo

Chuan-Xi Hu

Zhao-Wen Yan

Jing Chen

Guo-Qiang Chen

Ying Huang

Affiliations

Soon will be listed here.

Abstract

The regulation of the ubiquitously expressed protein phosphatase 2A (PP2A) is essential for various cellular functions such as cell proliferation, transformation, and fate determination. In this study, we demonstrate that the highly conserved protein in mammals, designated FAM122A, directly interacts with PP2A-Aα and B55α rather than B56α subunits, and inhibits the phosphatase activity of PP2A-Aα/B55α/Cα complex. Further, FAM122A potentiates the degradation of catalytic subunit PP2A-Cα with the increased poly-ubiquitination. In agreement, FAM122A silencing inhibits while its overexpression enhances cell growth and colony-forming ability. Collectively, we identify FAM122A as a new endogenous PP2A inhibitor and its physiological and pathophysiological significances warrant to be further investigated.

Citing Articles

Combining cryo-electron microscopy (cryo-EM) with orthogonal solution state methods to define the molecular basis of the phosphoprotein phosphatase family regulation and substrate specificity.

Peti W, Padi S, Page R Curr Opin Struct Biol. 2025; 91:102992.

PMID: 39951957 PMC: 11885005. DOI: 10.1016/j.sbi.2025.102992.

FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.

Wasserman J, Faezov B, Patel K, Kurimchak A, Palacio S, Glass D Nat Commun. 2024; 15(1):5776.

PMID: 38982062 PMC: 11233601. DOI: 10.1038/s41467-024-50015-7.

Increases in cyclin A/Cdk activity and in PP2A-B55 inhibition by FAM122A are key mitosis-inducing events.

Lacroix B, Vigneron S, Labbe J, Pintard L, Lionne C, Labesse G EMBO J. 2024; 43(6):993-1014.

PMID: 38378890 PMC: 10943098. DOI: 10.1038/s44318-024-00054-z.

High-resolution structures of two phosphatase-inhibitor complexes.

Nature. 2023; .

PMID: 38123854 DOI: 10.1038/d41586-023-03833-6.

Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.

Padi S, Vos M, Godek R, Fuller J, Kruse T, Hein J Nature. 2023; 625(7993):195-203.

PMID: 38123684 PMC: 10765524. DOI: 10.1038/s41586-023-06870-3.

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