Protein interactomes of protein phosphatase 2A B55 regulatory subunits reveal B55-mediated regulation of replication protein A under replication stress

Feifei Wang, Songli Zhu, Laura A. Fisher, Weidong Wang, Gregory G Oakley, Chunling Li, Aimin Peng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The specific function of PP2A, a major serine/threonine phosphatase, is mediated by regulatory targeting subunits, such as members of the B55 family. Although implicated in cell division and other pathways, the specific substrates and functions of B55 targeting subunits are largely undefined. In this study we identified over 100 binding proteins of B55α and B55β in Xenopus egg extracts that are involved in metabolism, mitochondria function, molecular trafficking, cell division, cytoskeleton, DNA replication, DNA repair, and cell signaling. Among the B55α and B55β-associated proteins were numerous mitotic regulators, including many substrates of CDK1. Consistently, upregulation of B55α accelerated M-phase exit and inhibited M-phase entry. Moreover, specific substrates of CDK2, including factors of DNA replication and chromatin remodeling were identified within the interactomes of B55α and B55β, suggesting a role for these phosphatase subunits in DNA replication. In particular, we confirmed in human cells that B55α binds RPA and mediates the dephosphorylation of RPA2. The B55-RPA association is disrupted after replication stress, consistent with the induction of RPA2 phosphorylation. Thus, we report here a new mechanism that accounts for both how RPA phosphorylation is modulated by PP2A and how the phosphorylation of RPA2 is abruptly induced after replication stress.

Original languageEnglish (US)
Article number2683
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Replication Protein A
Protein Phosphatase 2
Cell Division
DNA Replication
Phosphorylation
Proteins
Chromatin Assembly and Disassembly
Phosphoprotein Phosphatases
Xenopus
Cytoskeleton
Phosphoric Monoester Hydrolases
DNA Repair
Ovum
Carrier Proteins
Mitochondria
Up-Regulation

ASJC Scopus subject areas

  • General

Cite this

Protein interactomes of protein phosphatase 2A B55 regulatory subunits reveal B55-mediated regulation of replication protein A under replication stress. / Wang, Feifei; Zhu, Songli; Fisher, Laura A.; Wang, Weidong; Oakley, Gregory G; Li, Chunling; Peng, Aimin.

In: Scientific reports, Vol. 8, No. 1, 2683, 01.12.2018.

Research output: Contribution to journalArticle

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