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

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Feifei Wang ◽  
Songli Zhu ◽  
Laura A. Fisher ◽  
Weidong Wang ◽  
Gregory G. Oakley ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Protein A ◽  
Replication Stress ◽  
Replication Protein A ◽  
Replication Protein ◽  
Regulatory Subunits ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A-Dependent Dephosphorylation of Replication Protein A Is Required for the Repair of DNA Breaks Induced by Replication Stress

2009 ◽  
Vol 29 (21) ◽  
pp. 5696-5709 ◽  
Author(s):  
Junjie Feng ◽  
Timothy Wakeman ◽  
Sheila Yong ◽  
Xiaohua Wu ◽  
Sally Kornbluth ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Protein A ◽  
Replication Protein A ◽  
Dna Lesions ◽  
Replication Protein ◽  
Dna Breaks ◽  
Phosphatase 2A

ABSTRACT Eukaryotic genomic integrity is safeguarded by cell cycle checkpoints and DNA repair pathways, collectively known as the DNA damage response, wherein replication protein A (RPA) is a key regulator playing multiple critical roles. The genotoxic insult-induced phosphorylation of the 32-kDa subunit of human RPA (RPA32), most notably the ATM/ATR-dependent phosphorylation at T21 and S33, acts to suppress DNA replication and recruit other checkpoint/repair proteins to the DNA lesions. It is not clear, however, how the DNA damage-responsive function of phosphorylated RPA is attenuated and how the replication-associated activity of the unphosphorylated form of RPA is restored when cells start to resume the normal cell cycle. We report here that in cells recovering from hydroxyurea (HU)-induced genotoxic stress, RPA32 is dephosphorylated by the serine/threonine protein phosphatase 2A (PP2A). Interference with PP2A catalytic activity causes persistent RPA32 phosphorylation and increased HU sensitivity. The PP2A catalytic subunit binds to RPA following DNA damage and can dephosphorylate RPA32 in vitro. Cells expressing a RPA32 persistent phosphorylation mimetic exhibit normal checkpoint activation and reenter the cell cycle normally after recovery but display a pronounced defect in the repair of DNA breaks. These data indicate that PP2A-mediated RPA32 dephosphorylation is required for the efficient DNA damage repair.

Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling

2001 ◽  
Vol 353 (3) ◽  
pp. 417-439 ◽  
Author(s):  
Veerle JANSSENS ◽  
Jozef GORIS
Keyword(s):  
Protein Phosphatase ◽  
Cellular Localization ◽  
Protein Phosphatase 2A ◽  
Viral Proteins ◽  
Catalytic Subunit ◽  
Post Translational Modification ◽  
Regulatory Subunits ◽  
Regulatory Ability ◽  
Phosphatase 2A ◽  
Cycle Regulation

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon.

scholarly journals Antagonistic Regulation of Flowering Time through Distinct Regulatory Subunits of Protein Phosphatase 2A

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67987 ◽  
Author(s):  
Behzad Heidari ◽  
Dugassa Nemie-Feyissa ◽  
Saijaliisa Kangasjärvi ◽  
Cathrine Lillo
Keyword(s):  
Flowering Time ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunits ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A B55 and A Regulatory Subunits Interact with Nitrate Reductase and Are Essential for Nitrate Reductase Activation

2011 ◽  
Vol 156 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Behzad Heidari ◽  
Polina Matre ◽  
Dugassa Nemie-Feyissa ◽  
Christian Meyer ◽  
Odd Arne Rognli ◽  
...  
Keyword(s):  
Nitrate Reductase ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunits ◽  
Phosphatase 2A

scholarly journals Protein phosphatase 2A regulatory subunits perform distinct functional roles in the maize pathogenFusarium verticillioides

2013 ◽  
Vol 14 (5) ◽  
pp. 518-529 ◽  
Author(s):  
Joon-Hee Shin ◽  
Jung-Eun Kim ◽  
Martha Malapi-Wight ◽  
Yoon-E. Choi ◽  
Brian D. Shaw ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunits ◽  
Functional Roles ◽  
Phosphatase 2A

scholarly journals The Role of Protein Phosphatase 2A Catalytic Subunit Cα in Embryogenesis: Evidence from Sequence Analysis and Localization Studies

1999 ◽  
Vol 380 (9) ◽  
pp. 1117-1120 ◽  
Author(s):  
Jürgen Götz ◽  
Wilfried Kues
Keyword(s):  
Protein Phosphatase ◽  
Genomic Organization ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Catalytic Subunits ◽  
Regulatory Subunits ◽  
Phosphatase 2A ◽  
The Brain

AbstractProtein phosphatase 2A (PP2A) constitutes one of the major families of protein serine/threonine phosphatases found in all eukaryotic cells. PP2A holoenzymes are composed of a catalytic subunit complexed with a structural regulatory subunit of 65 kDa. These core subunits associate with regulatory subunits of various sizes to form different heterotrimers which have been purified and evaluated with regard to substrate specificity. In fully differentiated tissues PP2A expression levels are highest in the brain, however, relatively little is known about expression in the developing embryo.In order to determine the composition of PP2A catalytic subunits in the mouse, cDNAs were cloned and the genomic organization of PP2A Cα was determined.By a gene targeting approach in the mouse, we have previously shown that the absence of the major catalytic subunit of PP2A, Cα, resulted in embryonic lethality around embryonic day E6.5. No mesoderm was formed which implied that PP2A plays a crucial role in gastrulation.Here, we extended our studies and analyzed wildtype embryos for Cα expression at subsequent stages of development. After gastrulation is completed, we find high expression of Cα restricted to the neural folds, which suggests that PP2A plays an additional pivotal role in neurulation.

scholarly journals Localization of Saccharomyces cerevisiae Protein Phosphatase 2A Subunits throughout Mitotic Cell Cycle

2002 ◽  
Vol 13 (10) ◽  
pp. 3477-3492 ◽  
Author(s):  
Matthew S. Gentry ◽  
Richard L. Hallberg
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Protein Phosphatase ◽  
Fluorescent Protein ◽  
Protein Phosphatase 2A ◽  
Mitotic Cell ◽  
Regulatory Subunit ◽  
Regulatory Subunits ◽  
C Subunit ◽  
Phosphatase 2A

Protein phosphatase 2A (PP2A) regulates a broad spectrum of cellular processes. This enzyme is a collection of varied heterotrimeric complexes, each composed of a catalytic (C) and regulatory (B) subunit bound together by a structural (A) subunit. To understand the cell cycle dynamics of this enzyme population, we carried out quantitative and qualitative analyses of the PP2A subunits of Saccharomyces cerevisiae. We found the following: the level of each subunit remained constant throughout the cell cycle; there is at least 10 times more of one of the regulatory subunits (Rts1p) than the other (Cdc55p); Tpd3p, the structural subunit, is limiting for both catalytic and regulatory subunit binding. Using green fluorescent protein-tagged forms of each subunit, we monitored the sites of significant accumulation of each protein throughout the cell cycle. The two regulatory subunits displayed distinctly different dynamic localization patterns that overlap with the A and C subunits at the bud tip, kinetochore, bud neck, and nucleus. Using strains null for single subunit genes, we confirmed the hypothesis that regulatory subunits determine sites of PP2A accumulation. Although Rts1p and Tpd3p required heterotrimer formation to achieve normal localization, Cdc55p achieved its normal localization in the absence of either an A or C subunit.

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