Affinage

PPP2R2A

Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform · UniProt P63151

Length
447 aa
Mass
51.7 kDa
Annotated
2026-06-10
88 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP2R2A (B55α/PR55α) is the regulatory B subunit that targets the PP2A holoenzyme to specific substrates, defining a serine/threonine phosphatase activity central to cell-cycle control, signaling, and development (PMID:20711181, PMID:34661528). Its best-defined role is in mitotic exit: PP2A-B55α acts downstream of Cdk1 and the Mastl(Greatwall) kinase to dephosphorylate Cdk1 substrates and drive spindle breakdown and reassembly of the nuclear envelope, Golgi, and chromatin (PMID:20711181, PMID:21156286). B55α-PP2A confers substrate selectivity across a broad set of phosphoproteins—selectively dephosphorylating Akt-Thr308 but not Ser473 (PMID:18042541), the pocket protein p107 and FoxM1 to enforce G1/S and G2 control (PMID:20663872, PMID:21813648, PMID:23716589, PMID:23775125), ATM at DSB sites to govern homologous-recombination repair (PMID:23087057), SAMHD1-Thr592 to activate HIV-1 restriction during M/G1 (PMID:29884836), and c-Myc-Thr58 (with concomitant dephosphorylation of the ligase UBR5) to control Myc stability biphasically (PMID:41818150). Substrate recruitment is governed by a conserved short linear motif ([RK]-V-x-x-[VI]-R) that docks into a groove on the B55α β-propeller, a mechanism validated for p107 and TAU (PMID:34661528) and visualized by cryo-EM of B55α bound to inhibitory partners (PMID:40209703, PMID:40414499). This same surface is targeted by competitive regulators FAM122A and IER5, which occlude substrate docking (PMID:38982062, PMID:40209703), while the cofactor Eya3 binds the groove region to recruit and stimulate B55α-mediated dephosphorylation of Myc-Thr58 (PMID:38796066, PMID:40414499). B55α abundance is itself controlled by PHD2-mediated hydroxylation at Pro319 driving degradation (PMID:28329677) and by p53/FBXL20-dependent ubiquitination (PMID:34731788). Beyond proliferation, PP2A-B55α controls T-cell differentiation via GEF-H1/RhoA/ROCK signaling (PMID:33762326), cardiomyocyte HDAC5 trafficking (PMID:28343149), mitophagy and mitochondrial biogenesis through ULK1, TFEB, and PARIS (PMID:41042873), and epidermal/ectodermal development, where Ppp2r2a knockout mice are embryonic lethal with neural tube and epidermal barrier defects (PMID:32582689).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2007 High

    Established that B55α confers PP2A substrate selectivity at the level of individual phosphosites by showing it directs the holoenzyme to dephosphorylate Akt specifically at Thr308.

    Evidence Co-IP of endogenous holoenzymes with Akt, in vitro dephosphorylation, siRNA/overexpression in cells

    PMID:18042541

    Open questions at the time
    • Did not define the docking determinant on B55α
    • Physiological contexts of selective Thr308 control not mapped
  2. 2010 High

    Placed PP2A-B55α as the executor of mitotic exit downstream of Cdk1 inactivation, answering how dephosphorylation of Cdk1 substrates is coordinated to reverse mitotic phosphorylation.

    Evidence Genome-wide RNAi live-cell imaging screen, histone H1 phosphatase assay, importin-β1 co-purification, and genetic epistasis (Cdc20/Cdk1/Mastl) in mouse cells

    PMID:20711181 PMID:21156286

    Open questions at the time
    • Full substrate set during mitotic exit not enumerated
    • Mechanism of B55α activation timing relative to Mastl not resolved structurally
  3. 2010 Medium

    Defined B55α-specific regulation of pocket proteins, showing it restrains p107 and FoxM1 phosphorylation to control G1/S and G2 transitions.

    Evidence Co-IP, siRNA/overexpression with cell-cycle and FoxM1 activity readouts

    PMID:20663872 PMID:21813648

    Open questions at the time
    • Direct in vitro dephosphorylation of these substrates not shown in these studies
    • Selectivity among pocket proteins partially addressed
  4. 2012 High

    Extended B55α function to the DNA damage response by showing it dephosphorylates ATM at defined sites to regulate retention at DSBs and HR repair.

    Evidence Loss-of-function screen, biochemical dephosphorylation of defined ATM phosphosites, siRNA, HR repair assays

    PMID:23087057

    Open questions at the time
    • Recruitment mechanism to DSB sites not defined
    • Interplay with CHK2 feedback only partially mapped
  5. 2013 High

    Demonstrated that B55α itself is regulated by dephosphorylation as an activation switch, and linked it to stress and metabolic signaling (p107/FGF, EDD/p53, FOXO1).

    Evidence Reciprocal co-IP/MS, phosphorylation analysis of B55α, KD with phosphorylation/localization readouts in chondrocytes, β-cells, and cancer cells

    PMID:22417654 PMID:23499005 PMID:23716589 PMID:23775125

    Open questions at the time
    • Kinases driving B55α phosphorylation not fully identified
    • Quantitative affinity changes with phospho-state not structurally explained
  6. 2013 Medium

    Mapped a viral inhibitor (E4orf4) binding site on the B55α β-propeller above the substrate groove, distinguishing an allosteric/occlusion site from the substrate-docking surface.

    Evidence Structure-guided mutagenesis, IP, GST pulldown, cell death assays

    PMID:23530045 PMID:24244166

    Open questions at the time
    • No high-resolution structure of the E4orf4-B55α complex in these studies
    • Relationship to endogenous regulators unclear at the time
  7. 2018 High

    Connected mitotic-exit dephosphorylation to antiviral immunity by showing B55α dephosphorylates SAMHD1-Thr592 at M/G1 to activate HIV-1 restriction.

    Evidence Proteomics, co-IP, cell-cycle synchronization, HIV-1 infection assays, validation in macrophages

    PMID:29884836

    Open questions at the time
    • Regulation in fully non-cycling cells incompletely defined
    • Direct SLiM in SAMHD1 not mapped here
  8. 2021 High

    Resolved the molecular grammar of substrate recruitment by defining a conserved SLiM ([RK]-V-x-x-[VI]-R) that docks into the B55α groove and dictates dephosphorylation of proximal phosphosites.

    Evidence Mutagenesis of the SLiM in p107 and TAU, in vitro and cellular dephosphorylation, data-guided computational modeling

    PMID:34661528

    Open questions at the time
    • Computational model not yet an experimental structure
    • How phosphosite presentation distance is tuned remains partial
  9. 2021 High

    Defined immune and developmental roles in vivo: B55α activates GEF-H1/RhoA/ROCK to drive Th1/Th17 differentiation, and is essential for ectodermal/epidermal development.

    Evidence T-cell conditional KO with RhoA activity and differentiation assays; CRISPR KO mice with developmental phenotyping

    PMID:32582689 PMID:33762326

    Open questions at the time
    • Tissue-specific substrate repertoires not exhaustively defined
    • Embryonic lethality limits adult tissue analysis
  10. 2024 High

    Established competitive inhibition as a core regulatory logic: FAM122A occludes the substrate groove to block CDK-substrate dephosphorylation, controlling cell-cycle checkpoints.

    Evidence Structure prediction, mutagenesis, in vitro competition assays, CRISPR KO with checkpoint and DDR readouts

    PMID:38982062

    Open questions at the time
    • Competition kinetics versus diverse substrates not fully quantified
    • Regulation of FAM122A availability not addressed
  11. 2025 High

    Provided experimental structures of the B55α regulatory interface, showing IER5 and Eya3 engage the substrate-recruitment surface as inhibitor and recruiter respectively, with translation to peptide-based modulation of Myc.

    Evidence Cryo-EM of B55α-IER5-N50 and B55α-Eya3, in vitro pTau/pMyc dephosphorylation, mutagenesis, inhibitory peptide B55i in TNBC cells

    PMID:38796066 PMID:40209703 PMID:40414499

    Open questions at the time
    • Full catalytic-cycle structure with bound substrate not captured
    • Selectivity of Eya3 stimulation across substrates beyond Myc not defined
  12. 2025 Medium

    Expanded B55α into mitochondrial quality control and tumor immunity, regulating mitophagy/biogenesis via ULK1/TFEB/PARIS and the cGAS-STING/PD-L1 axis.

    Evidence Multi-omics, phosphoproteomics, nuclear fractionation, Drosophila PD model; KD/heterozygous cells with cGAS-STING and PD-L1 assays in lung cancer models

    PMID:41042873 PMID:41411055

    Open questions at the time
    • Direct substrates within mitophagy and STING pathways not all defined
    • Mechanism of cytosolic DNA accumulation upon deficiency unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the single B55α groove discriminates among its many SLiM-bearing substrates and competitive regulators in a given cellular context remains unresolved.
  • No experimental structure of B55α with a bound physiological substrate phosphosite
  • Combinatorial rules governing substrate prioritization in vivo unknown
  • Quantitative competition between FAM122A, IER5, Eya3, and substrates not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3
Partners
AKT1ATMEYA3FAM122AFOXM1IER5SAMHD1UBR5
Complex memberships
PP2A holoenzyme (A-B55α-C trimer)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 B55α (PPP2R2A) directly interacts with Akt and targets the PP2A holoenzyme to Akt, selectively dephosphorylating Akt at Thr-308 but not Ser-473, thereby regulating cell proliferation and survival. Confirmed by co-immunoprecipitation of endogenous PP2A-AB55C holoenzymes with Akt, in vitro pulldown, in vitro dephosphorylation assays, overexpression, and siRNA knockdown experiments. Co-immunoprecipitation, in vitro pulldown, in vitro dephosphorylation assay, siRNA knockdown, overexpression The Journal of biological chemistry High 18042541
2010 PP2A-B55α trimeric complex is a key regulator of mitotic exit in human cells, required for mitotic spindle breakdown and postmitotic reassembly of nuclear envelope, Golgi apparatus, and decondensed chromatin. PP2A-B55α functions downstream of Cdk1 inactivation. Mitotic PP2A-B55α has reduced phosphatase activity toward Cdk1 substrate histone H1 and is hyper-phosphorylated on all subunits. Mitotic PP2A complexes co-purify with importin-β1, and co-depletion of importin-β1 delays mitotic exit synergistically. RNAi live-cell imaging screen, chemically induced mitotic exit assay, phosphatase activity assay toward histone H1, co-purification/mass spectrometry, double RNAi knockdown Nature cell biology High 20711181
2010 Mitotic exit in Cdk1-inactivated cells depends on activity of PP2A complexes containing B55α or B55δ regulatory subunits, placing PP2A/B55α downstream of Cdk1 and the kinase Mastl (Greatwall) in the mitotic exit pathway. Demonstrated by genetic epistasis in mouse embryonic and adult cells. Genetically engineered mice, genetic epistasis (Cdc20 ablation + Cdk1/Mastl inactivation) Cancer cell High 21156286
2012 PPP2R2A-containing PP2A complexes directly dephosphorylate ATM at S367, S1893, and S1981, regulating ATM retention at double-strand break (DSB) sites. Loss of PPP2R2A increases ATM phosphorylation and CHK2 activity, leading to G1/S arrest and downregulation of BRCA1 and RAD51, impairing homologous recombination repair. Loss-of-function screen, biochemical dephosphorylation assays, siRNA knockdown, cell-cycle analysis, HR repair assays Cancer research High 23087057
2013 Upon glutamine deprivation, B55α is induced in a ROS-dependent manner and activates p53 through direct interaction with and dephosphorylation of EDD (a negative regulator of p53). α4 promotes assembly of an adaptive PP2A complex containing B55α under these conditions. The B55α-EDD-p53 pathway is essential for cancer cell survival under low glutamine conditions. Co-immunoprecipitation, biochemical interaction assays, RNAi knockdown, in vitro and in vivo tumor growth assays Molecular cell High 23499005
2010 B55α PP2A holoenzyme plays a major role in restricting phosphorylation of p107 (retinoblastoma-related protein) and inducing its activation in human cells. Targeted selectivity exists between pocket proteins and distinct PP2A holoenzymes. Co-immunoprecipitation, siRNA knockdown, overexpression, cell-cycle analysis The Journal of biological chemistry Medium 20663872
2011 B55α (PPP2R2A) interacts with FoxM1 transcription factor and promotes its dephosphorylation and inactivation, antagonizing Cyclin A/Cdk-dependent activation of FoxM1 to restrict its activity to G2 phase. Overexpression of B55α decreases FoxM1 activity; depletion leads to premature FoxM1 activation dependent on Cyclin A/Cdk phosphorylation. Co-immunoprecipitation, overexpression, siRNA knockdown, FoxM1 activity assays The Journal of biological chemistry Medium 21813648
2012 B55α-containing PP2A holoenzyme (identified by chemical cross-linking and mass spectrometry) dephosphorylates FOXO1 at Thr24 and Ser256 to promote FOXO1 nuclear translocation in pancreatic islet β-cells under oxidative stress. Knockdown of B55α inhibits FOXO1 nuclear translocation and attenuates oxidative stress-induced cell death. Chemical cross-linking, mass spectrometry, co-immunoprecipitation, siRNA knockdown, nuclear fractionation The Biochemical journal High 22417654
2013 PP2A-B55α holoenzyme is responsible for FGF-induced p107 dephosphorylation and growth arrest in chondrocytes. B55α binds p107 with higher affinity in its dephosphorylated state; only B55α (not other B subunits) binds p107. FGF induces dephosphorylation of B55α itself on multiple serine residues, dramatically increasing its affinity for the PP2A A/C dimer and p107. Co-immunoprecipitation, siRNA knockdown, phosphorylation analysis, cell cycle analysis Molecular and cellular biology High 23716589 23775125
2013 Reciprocal solution-based mass spectrometry identified PP2A/B55α complex as a major component of p107 complexes in chondrocytes. FGF1 triggers rapid accumulation of p107-PP2A/B55α complexes coinciding with p107 dephosphorylation and nuclear accumulation, leading to cell cycle exit. B55α knockdown delays FGF1-induced dephosphorylation of p107. Reciprocal mass spectrometry, co-immunoprecipitation, siRNA knockdown, nuclear fractionation, chromatin immunoprecipitation Molecular and cellular biology High 23775125
2013 Adenovirus E4orf4 binds across the putative substrate binding groove of B55α such that the substrate p107 can no longer interact with PP2A-B55α, thus inhibiting PP2A activity by preventing substrate access. E4orf4 binding was mapped to the α1,α2 helices of B55α using mutagenesis and structural prediction; loss of binding reduces E4orf4-induced cell death. Structure-guided mutagenesis, immunoprecipitation, GST pulldown, cell death assays PLoS pathogens Medium 24244166
2013 E4orf4 binding site in PP2A-B55α maps to α1 and α2 helices (blade 1/2 region) of the seven-bladed β-propeller. This site lies above the substrate binding groove and does not overlap it. Loss of E4orf4 binding at this site reduces E4orf4-induced cell death. Bioinformatics, mutagenesis, immunoprecipitation, GST pulldown The Journal of biological chemistry Medium 23530045
2014 PR55α-PP2A specifically dephosphorylates c-Jun at T239, promoting c-Jun binding to chromatin at genes regulating tumor cell migration and invasion, without affecting phosphorylation at S63. PR55α-PP2A thus enhances AP-1 transcriptional activity and tumor cell migration/invasion. Co-immunoprecipitation, phosphorylation-specific antibodies, chromatin immunoprecipitation, migration/invasion assays, siRNA knockdown Oncogene Medium 24632621
2014 F-box protein FBXL16 binds PP2A containing B55α specificity subunit (PP2A-B55α) and negatively regulates its activity. FBXL16 negatively regulates phosphorylation of the established PP2A-B55α substrate vimentin as shown by phosphoproteomics. Shotgun mass spectrometry, phosphoproteomics, siRNA screen Molecular & cellular proteomics Medium 24390425
2015 B55α mediates PP2A/Plk1 association and dephosphorylation of Plk1 at Thr-210 in response to DNA damage in Xenopus egg extracts. PP2A-B55α association with Plk1 increases after DNA damage in an ATM/ATR and checkpoint kinase-dependent manner. Xenopus egg extract biochemistry, co-immunoprecipitation, phosphatase activity assays, DNA damage induction Cell cycle Medium 25483054
2017 β-Adrenoceptor stimulation induces B55α-PP2A-mediated dephosphorylation of HDAC5 at Ser259/Ser498, leading to HDAC5 nuclear accumulation in cardiomyocytes. B55α specifically interacts with HDAC5 (and the PP2A catalytic and scaffolding subunits), and this interaction increases >3-fold with isoproterenol. Knockdown of B55α attenuates isoproterenol-induced HDAC5 dephosphorylation. Co-immunoprecipitation, site-directed mutagenesis, siRNA knockdown, 3D confocal microscopy localization assay Journal of the American Heart Association Medium 28343149
2017 PHD2 promotes degradation of B55α by hydroxylating it at proline 319. Conversely, B55α-associated PP2A promotes partial deactivation of PHD2. In glucose-starved conditions, PHD2 reduces B55α protein levels, correlating with breast cancer cell death; PHD2 silencing rescues B55α and prevents apoptosis. Hydroxylation assay, siRNA knockdown, overexpression, xenograft tumor model Cell reports Medium 28329677
2018 SAMHD1 dephosphorylation at T592 is mediated by PP2A-B55α holoenzymes during mitotic exit (M/G1 transition), rendering SAMHD1 antivirally active against HIV-1. Identified using complementary proteomics and biochemical approaches. PP2A-B55α also controls SAMHD1 pT592 levels in non-cycling monocyte-derived macrophages. Proteomics, biochemical co-immunoprecipitation, cell cycle synchronization, HIV-1 infection assays, siRNA knockdown Nature communications High 29884836
2019 PR55α inhibits the MOB1-triggered autoactivation of LATS1/2 kinases (core Hippo pathway members) and directly interacts with YAP, leading to YAP activation and promotion of anchorage-independent growth in pancreatic cancer cells. Co-immunoprecipitation, siRNA knockdown, kinase activity assays, gene transcription assays, anchorage-independent growth assays Oncogenesis Medium 31659153
2020 PPP2R2A negatively regulates translation of c-Myc protein, and PPP2R2A deficiency elevates replication stress by upregulating c-Myc activity, rendering cells reliant on the ATR/CHK1 axis for survival. Identified in a genome-wide loss-of-function screen. Genome-wide shRNA pooled screen, c-Myc protein level analysis, replication dynamics assays, in vitro and in vivo drug sensitivity assays Cancer research Medium 32522823
2020 AMOTL2 is a novel binding partner of PPP2R2A in NSCLC cells. AMOTL2 binds PPP2R2A in the cytoplasm and reduces its nuclear localization, thereby inhibiting PPP2R2A-mediated dephosphorylation of JUN at T239 and increasing JUN T239 phosphorylation. This AMOTL2-PPP2R2A-JUN axis regulates cell proliferation. Mass spectrometry, co-immunoprecipitation, GST pulldown, immunofluorescence, CRISPR/Cas9 screen Biochimica et biophysica acta. Molecular cell research Medium 32950569
2020 PP2A-B55α complex restrains PHD2 activity in endothelial cells, promoting EC survival in a HIF-dependent manner, and dephosphorylates p38, protecting ECs against cell stress. B55α inhibition leads to EC apoptosis and vessel pruning. Genetic EC-specific B55α deficiency (knockout mouse model), biochemical phosphatase assays, HIF pathway analysis, p38 phosphorylation analysis, in vivo vascular imaging Circulation research Medium 32527198
2021 PP2A/B55α substrate recruitment is mediated by a conserved short linear motif (SLiM) 'HxRVxxV619-625' in substrate p107 (region R1, residues 615-626) that is necessary for B55α binding and dephosphorylation of proximal pSer-615 in vitro and in cells. A related SLiM '[RK]-V-x-x-[VI]-R' is present in numerous B55α substrates including TAU; mutation of conserved SLiM residues in TAU dramatically inhibits dephosphorylation by PP2A/B55α. A computational model details the interaction of residues from the SLiM, the B55α groove, and phosphosite presentation. Molecular biology, mutagenesis, in vitro dephosphorylation assays, cellular phosphorylation assays, data-guided computational modeling eLife High 34661528
2021 PPP2R2A binds to, dephosphorylates, and activates GEF-H1 at Ser885, increasing RhoA-GTP levels and ROCK activity in T cells, thereby enhancing Th1 and Th17 differentiation. T cell-specific PPP2R2A knockout mice showed reduced Th1/Th17 differentiation and less autoimmunity. Co-immunoprecipitation, phosphorylation assays, T cell-specific conditional knockout mice, RhoA activity assay, T cell differentiation assays Journal of immunology High 33762326
2021 p53 negatively regulates PR55α protein stability via FBXL20 (a p53-target gene encoding an SCF E3 ubiquitin ligase component). Loss of p53 function leads to reduced FBXL20 expression, decreased PR55α ubiquitination, and increased PR55α protein stability; increased PR55α dephosphorylates c-Myc at T58 (a known PR55α substrate), increasing c-Myc stability. siRNA knockdown, gene deletion, HPV-E6-mediated degradation, mutant p53 expression, ubiquitination assays, co-immunoprecipitation Neoplasia Medium 34731788
2020 Ppp2r2a homozygous knockout mice are embryonic lethal and display neural tube defects, syndactyly, and severe epidermal defects including impaired epidermal barrier acquisition, thin/poorly differentiated stratified epithelium, reduced integrin and basement membrane protein expression, and aberrant junction proteins—establishing PP2A-B55α as an essential regulator of ectodermal/epidermal development. CRISPR/Cas9 knockout mouse generation, embryonic staging, immunohistochemistry, immunofluorescence Frontiers in cell and developmental biology High 32582689
2017 PP2A-B55α is required for meiosis in mouse oocytes. Knockdown of PP2A-B55α leads to abnormal asymmetric division, disordered spindle dynamics, chromosome congression defects, increased aneuploidy, and DNA damage response induction. In fertilized zygotes, knockdown impairs development to blastocyst stage by inducing sustained DNA damage, apoptosis, and inhibiting proliferation. siRNA knockdown in mouse oocytes, immunofluorescence for spindle/chromosome analysis, aneuploidy scoring, blastocyst development assays Oncotarget Medium 28439046
2023 PP2A-B55α holoenzyme is the major serine/threonine phosphatase regulating the phosphorylation status of desmoplakin (DP) C-terminus in keratinocytes. PP2A-B55α interacts with DP at intercellular membranes (shown by 2D/3D epidermal models and human skin samples) and is required for maintaining strong desmosome-mediated intercellular adhesion. Chemical and genetic inhibition, co-immunoprecipitation, immunofluorescence in 2D/3D epidermal models and human skin, adhesion strength assays Scientific reports Medium 37543698
2024 FAM122A functions as a competitive inhibitor of B55α/PP2A. FAM122A binds B55α through a conserved SLiM '[RK]-V-x-x-[VI]-R' motif that blocks substrate docking; FAM122A competitively inhibits CDK substrate binding and dephosphorylation by B55α/PP2A in cell lysates. FAM122A deficiency reduces cell proliferation, cell cycle progression, and hinders G1/S and intra-S phase checkpoints; FAM122A-KO attenuates CHK1 and CHK2 activation in response to replication stress. Computational structure prediction, mutagenesis, in vitro competition assay with cell lysates, CRISPR/Cas9 KO, cell cycle analysis, DNA damage response assays Nature communications High 38982062
2025 Cryo-EM structure of PP2A-B55α with IER5 N-terminal region (IER5-N50) reveals that IER5-N50 occludes the substrate recruitment surface on B55α. IER5-N50 inhibits PP2A/B55α-catalyzed dephosphorylation of pTau in biochemical assays. Mutations disrupting the IER5-B55α interface abolish co-immunoprecipitation of PP2A-B55α. IER5 antagonism of B55α in keratinocytes is required for KRT1 expression. Cryo-EM structure determination, in vitro dephosphorylation assay, mutagenesis, co-immunoprecipitation, IER5 knockout cell rescue experiments Cell chemical biology High 40209703
2024 Eya3 directly interacts with the N-terminal domain of Myc and recruits PP2A-B55α to dephosphorylate pT58 on Myc, increasing Myc stability. Eya3 increases Ser/Thr phosphatase activity of PP2A-B55α (but not PP2A-B56α). The Eya3 NTD (~250 aa, fully disordered) uses a 38-residue segment to interact with B55α. Knockdown/phosphoproteomics shows Eya3 and B55α share highly similar phosphosite motifs (preference for Ser/Thr-Pro). The cancer hotspot mutation MycP59A enhances Eya3-PP2A-B55α dephosphorylation of pT58. Biochemical co-IP, pulldown, in vitro phosphatase activity assay, NMR (disordered domain characterization), phosphoproteomics, mutagenesis, cell proliferation assays The Journal of biological chemistry High 38796066
2025 Cryo-EM structures of PP2A-B55α bound to Eya3 show that Eya3 binds B55α through an extended peptide in the Eya3 NTD that occupies a similar area on B55α as substrates and peptide inhibitors. An inhibitory peptide B55i also occludes this surface. B55i inhibits the B55α-Eya3 interaction in vitro and increases Myc pT58, decreasing Myc levels in TNBC cells. Cryo-EM structure determination, in vitro interaction assay, cellular Myc phosphorylation assays The Journal of biological chemistry High 40414499
2013 Ppp2r2a is required for Connexin-43 dephosphorylation at Serine 368 during epidermal barrier acquisition. Knockdown of Ppp2r2a prevented plasma membrane co-localization and interaction between Connexin 43 and Zo-1, and increased Cx43 phosphorylation at Ser368, implicating PP2A-B55α in regulating tight junction formation through Cx43 dephosphorylation. siRNA knockdown, co-immunoprecipitation, immunofluorescence, epidermal barrier assay Experimental dermatology Medium 24433183
2018 PPP2R2A interacts with GFPT1/2 (glutamine:fructose-6-phosphate amidotransferase 1/2) and dephosphorylates GFPT2 specifically (but not GFPT1); knockdown of PPP2R2A enhanced GFPT2 phosphorylation and promoted total cellular O-GlcNAcylation in breast cancer cells. Interaction confirmed by GST pulldown, co-IP, and immunofluorescence. Tandem affinity purification, mass spectrometry, GST pulldown, co-immunoprecipitation, immunofluorescence, O-GlcNAcylation assay, shRNA knockdown Sheng wu gong cheng xue bao (Chinese journal of biotechnology) Medium 29943541
2023 VPA (a histone deacetylase inhibitor) promotes PPP2R2A-mediated dephosphorylation of Chk1 at Ser317 and Ser345, accelerating G2/M progression. The effect of VPA on PPP2R2A operates at the post-transcriptional level through HDAC1/2. PPP2R2A residues D197 and N181 are essential for PPP2R2A-Chk1 signaling. Phosphorylation assays, mutagenesis, co-immunoprecipitation, cell cycle analysis, in vivo experiments Cell death & disease Medium 36781846
2025 PP2A-B55α/PPP2R2A is identified as a Parkin-dependent regulator of mitochondrial number. Upon mitochondrial damage, PP2A-B55α regulates early mitophagy by releasing ULK1 from its inhibitory regulation, and later (2-4 hours) promotes nuclear translocation of TFEB to support mitophagy. PP2A-B55α also controls mitochondrial biogenesis by stabilizing PARIS (a PGC-1α inhibitor and Parkin substrate). PP2A-B55α targeting rescues neurodegenerative phenotypes in a Drosophila Parkinson's disease model. Unbiased LC-MS/MS and transcriptomics, phosphoproteomics, genetic manipulation, nuclear fractionation, in vivo Drosophila model Science advances High 41042873
2025 PP2A-B55α directly dephosphorylates c-Myc at Thr58 and regulates two distinct c-Myc degradation pathways in a biphasic manner: B55α suppression increases Thr58 phosphorylation and enhances FBXW7-dependent degradation, while B55α overexpression promotes Thr58-independent UBR5-mediated degradation. PP2A-B55α complex also binds and dephosphorylates UBR5. B55δ shows weaker UBR5 binding affinity and fails to induce c-Myc degradation. Biochemical dephosphorylation assays, co-immunoprecipitation, mutagenesis, ubiquitination assays, overexpression/knockdown Proceedings of the National Academy of Sciences High 41818150
2025 PPP2R2A deficiency causes cytosolic DNA accumulation leading to cGAS-STING-type I IFN pathway activation. PPP2R2A deficiency elevates PD-L1 expression via GSK-3β-dependent and STING-dependent mechanisms, modulating the tumor immune microenvironment. siRNA knockdown, PPP2R2A heterozygous cell lines, cGAS-STING pathway assays, PD-L1 expression analysis, GSK-3β inhibition, mouse lung cancer model, immune cell profiling The Journal of clinical investigation Medium 41411055
2024 PPP2R2A deficiency in NSCLC promotes epithelial-mesenchymal transition (EMT) and metastatic behavior. Mechanistically, PP2A B55α inhibits EMT by downregulating SNAI2 (Slug) expression via the GSK3β-β-catenin pathway. PPP2R2A deficiency also increases the cancer stem cell population and enhances drug resistance. shRNA knockdown, CRISPR/Cas9 homozygous/hemizygous depletion, bulk RNA-sequencing, GSEA, EMT marker analysis, invasion/migration assays, tail vein metastasis assay Cancer letters Medium 38986733
2024 PPP2R2A controls NAD+ biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. PPP2R2A deficiency promotes NAD+ biosynthesis; elevated NR inhibits Th17 and promotes Treg differentiation by PARylating histone H1.2, altering Foxp3 and Il17a locus occupancy. T cell-specific PPP2R2A knockout (lupus-prone mice), metabolomics, chromatin immunoprecipitation, cytokine assays, NR supplementation experiments Cell reports Medium 38889006
2024 PR55α is a potent inhibitor of p16 transcription; ectopic PR55α expression in normal pancreatic cells inhibits p16 transcription, increases RB phosphorylation, and blocks IR-induced cellular senescence. This function is p53-independent and specifically affects p16 (not p14/ARF). Ectopic expression, shRNA knockdown, RT-PCR for p16 expression, RB phosphorylation analysis, senescence assays (SA-β-gal, BrdU incorporation) Aging Medium 38441530

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt. The Journal of biological chemistry 322 18042541
2010 Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells. Nature cell biology 276 20711181
2010 Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase. Cancer cell 181 21156286
2013 The B55α subunit of PP2A drives a p53-dependent metabolic adaptation to glutamine deprivation. Molecular cell 135 23499005
2012 Loss of PPP2R2A inhibits homologous recombination DNA repair and predicts tumor sensitivity to PARP inhibition. Cancer research 110 23087057
2014 Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2 activation by targeting PPP2R2A. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 77 23959478
2016 miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells. Journal of cellular and molecular medicine 76 26800397
2011 Low expression of PP2A regulatory subunit B55α is associated with T308 phosphorylation of AKT and shorter complete remission duration in acute myeloid leukemia patients. Leukemia 71 21660042
2016 PR55α Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling. Cancer research 61 26893480
2011 Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study. Cancer genetics 57 21872824
2018 Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit. Nature communications 54 29884836
2019 PR55α regulatory subunit of PP2A inhibits the MOB1/LATS cascade and activates YAP in pancreatic cancer cells. Oncogenesis 38 31659153
2020 A Genome-Wide Pooled shRNA Screen Identifies PPP2R2A as a Predictive Biomarker for the Response to ATR and CHK1 Inhibitors. Cancer research 34 32522823
2021 The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway. Journal of immunology (Baltimore, Md. : 1950) 33 33762326
2021 Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A. International journal of nanomedicine 33 34556984
2015 MicroRNA-136 Promotes Vascular Muscle Cell Proliferation Through the ERK1/2 Pathway by Targeting PPP2R2A in Atherosclerosis. Current vascular pharmacology 33 25409743
2010 B55alpha PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation. The Journal of biological chemistry 33 20663872
2015 miR-892a regulated PPP2R2A expression and promoted cell proliferation of human colorectal cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 26054685
2020 B55α/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling: A Complementary Approach To Disrupt Pathological Vessels? Circulation research 31 32527198
2021 PP2A/B55α substrate recruitment as defined by the retinoblastoma-related protein p107. eLife 30 34661528
2019 MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A. Bioscience reports 30 31221814
2017 β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation. Journal of the American Heart Association 30 28343149
2014 The protein phosphatase 2A regulatory subunit B55α is a modulator of signaling and microRNA expression in acute myeloid leukemia cells. Biochimica et biophysica acta 30 24858343
2011 Protein phosphatase 2A (B55α) prevents premature activation of forkhead transcription factor FoxM1 by antagonizing cyclin A/cyclin-dependent kinase-mediated phosphorylation. The Journal of biological chemistry 30 21813648
2015 miR-222 overexpression may contribute to liver fibrosis in biliary atresia by targeting PPP2R2A. Journal of pediatric gastroenterology and nutrition 29 25238119
2015 Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. Cell cycle (Georgetown, Tex.) 29 25483054
2012 The B55α-containing PP2A holoenzyme dephosphorylates FOXO1 in islet β-cells under oxidative stress. The Biochemical journal 29 22417654
2015 Altered PPP2R2A and Cyclin D1 expression defines a subgroup of aggressive luminal-like breast cancer. BMC cancer 28 25879784
2013 The B55α regulatory subunit of protein phosphatase 2A mediates fibroblast growth factor-induced p107 dephosphorylation and growth arrest in chondrocytes. Molecular and cellular biology 28 23716589
2017 PHD2 Targeting Overcomes Breast Cancer Cell Death upon Glucose Starvation in a PP2A/B55α-Mediated Manner. Cell reports 27 28329677
2020 microRNA-665 is down-regulated in gastric cancer and inhibits proliferation, invasion, and EMT by targeting PPP2R2A. Cell biochemistry and function 25 31923339
2016 Novel B55α-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest. Oncotarget 25 27531894
2013 Activation of p107 by fibroblast growth factor, which is essential for chondrocyte cell cycle exit, is mediated by the protein phosphatase 2A/B55α holoenzyme. Molecular and cellular biology 25 23775125
2020 Ppp2r2a Knockout Mice Reveal That Protein Phosphatase 2A Regulatory Subunit, PP2A-B55α, Is an Essential Regulator of Neuronal and Epidermal Embryonic Development. Frontiers in cell and developmental biology 24 32582689
2014 F-box protein FBXL16 binds PP2A-B55α and regulates differentiation of embryonic stem cells along the FLK1+ lineage. Molecular & cellular proteomics : MCP 24 24390425
2017 Insufficient activation of Akt upon reperfusion because of its novel modification by reduced PP2A-B55α contributes to enlargement of infarct size by chronic kidney disease. Basic research in cardiology 23 28421341
2015 miR-136 modulates TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes. BioMed research international 23 25654102
2022 A cannabidiol aminoquinone derivative activates the PP2A/B55α/HIF pathway and shows protective effects in a murine model of traumatic brain injury. Journal of neuroinflammation 22 35810304
2015 Upregulation of miR-556-5p promoted prostate cancer cell proliferation by suppressing PPP2R2A expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 26297546
2016 Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer. Oncotarget 20 26848620
2014 PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity. Oncogene 20 24632621
2020 AMOTL2 inhibits JUN Thr239 dephosphorylation by binding PPP2R2A to suppress the proliferation in non-small cell lung cancer cells. Biochimica et biophysica acta. Molecular cell research 19 32950569
2018 MKAD-21 Suppresses the Oncogenic Activity of the miR-21/PPP2R2A/ERK Molecular Network in Bladder Cancer. Molecular cancer therapeutics 19 29703843
2016 Haploinsufficiency of the Insulin Receptor in the Presence of a Splice-Site Mutation in Ppp2r2a Results in a Novel Digenic Mouse Model of Type 2 Diabetes. Diabetes 19 26868295
2021 LncRNA-HCG18 regulates the viability, apoptosis, migration, invasion and epithelial-mesenchymal transition of papillary thyroid cancer cells via regulating the miR-106a-5p/PPP2R2A axis. Pathology, research and practice 18 33798913
2018 Upregulation of miR-614 promotes proliferation and inhibits apoptosis in ovarian cancer by suppressing PPP2R2A expression. Molecular medicine reports 17 29532877
2017 Protein phosphatase 2A regulatory subunit B55α functions in mouse oocyte maturation and early embryonic development. Oncotarget 17 28439046
2013 Identification of the adenovirus E4orf4 protein binding site on the B55α and Cdc55 regulatory subunits of PP2A: Implications for PP2A function, tumor cell killing and viral replication. PLoS pathogens 17 24244166
2019 Overexpression of miR-222-3p Promotes the Proliferation and Inhibits the Apoptosis of Diffuse Large B-Cell Lymphoma Cells via Suppressing PPP2R2A. Technology in cancer research & treatment 16 31829105
2006 Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma. Neoplasia (New York, N.Y.) 16 16790090
2013 Structure- and modeling-based identification of the adenovirus E4orf4 binding site in the protein phosphatase 2A B55α subunit. The Journal of biological chemistry 14 23530045
2021 PPP2R2A affects embryonic implantation by regulating the proliferation and apoptosis of Hu sheep endometrial stromal cells. Theriogenology 13 34619436
2010 Genetic analysis of B55alpha/Cdc55 protein phosphatase 2A subunits: association with the adenovirus E4orf4 protein. Journal of virology 13 21047956
2024 PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer. Cancer letters 11 38986733
2023 A novel PPP2R2A::PRKD1 fusion in a cribriform adenocarcinoma of salivary gland. Genes, chromosomes & cancer 10 36625487
2020 Hsa-MiR-590-3p Promotes the Malignancy Progression of Pancreatic Ductal Carcinoma by Inhibiting the Expression of p27 and PPP2R2A via G1/S Cell Cycle Pathway. OncoTargets and therapy 10 33149617
2020 Hepsin Promotes Epithelial-Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer. OncoTargets and therapy 9 33268993
2024 PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation. Aging 8 38441530
2024 The PP2A regulatory subunit PPP2R2A controls NAD+ biosynthesis to regulate T cell subset differentiation in systemic autoimmunity. Cell reports 8 38889006
2024 FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs. Nature communications 8 38982062
2023 Silencing of microRNA-106b-5p prevents doxorubicin-mediated cardiotoxicity through modulation of the PR55α/YY1/sST2 signaling axis. Molecular therapy. Nucleic acids 8 37234747
2022 Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats. Translational stroke research 8 35419730
2023 PPP2R2A promotes testosterone secretion in Hu sheep Leydig cells via activation of the AKT/mTOR signaling pathway. Journal of molecular endocrinology 7 36883561
2021 Circ_0137287 suppresses cell tumroigenesis and aerobic glycolysis in papillary thyroid carcinoma through miR-183-5p/PPP2R2A axis. Cytotechnology 7 34149180
2024 Biochemical characterization of the Eya and PP2A-B55α interaction. The Journal of biological chemistry 6 38796066
2023 PME-1 sensitizes glioblastoma cells to oxidative stress-induced cell death by attenuating PP2A-B55α-mediated inactivation of MAPKAPK2-RIPK1 signaling. Cell death discovery 6 37500619
2023 PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus. Scientific reports 5 37543698
2021 miR-660 promotes liver cancer cell proliferation by targeting PPP2R2A. Experimental and therapeutic medicine 5 33986848
2021 p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase. Neoplasia (New York, N.Y.) 5 34731788
2013 The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin-43 dephosphorlyation during epidermal barrier acquisition. Experimental dermatology 5 24433183
2025 Molecular mechanism of PP2A/B55α phosphatase inhibition by IER5. Cell chemical biology 4 40209703
2024 Molecular Mechanism of PP2A/B55α Phosphatase Inhibition by IER5. bioRxiv : the preprint server for biology 4 37693604
2023 VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU. Cell death & disease 4 36781846
2022 FBXL16 Promotes Endometrial Progesterone Resistance via PP2AB55 /Cyclin D1 Axis in Ishikawa. Journal of immunology research 4 36106050
2024 Low PPP2R2A expression promotes sensitivity to CHK1 inhibition in high-grade serous ovarian cancer. Theranostics 3 39659585
2021 Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma. Cancer cell international 3 33588847
2025 The PP2A-B55α phosphatase is a master regulator of mitochondrial degradation and biogenesis. Science advances 2 41042873
2025 PPP2R2A insufficiency enhances PD-L1 immune checkpoint blockade efficacy in lung cancer through cGAS-STING activation. The Journal of clinical investigation 2 41411055
2024 PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells. Cell division 2 38734666
2018 [PPP2R2A binds and dephosphorylates GFPT2 in breast cancer cells]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 2 29943541
2024 Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α. npj metabolic health and disease 1 40603585
2026 Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels. Proceedings of the National Academy of Sciences of the United States of America 0 41818150
2025 Characterization of RNF144B and PPP2R2A identified by a novel approach using TCGA data in ovarian cancer. Scientific reports 0 39948107
2025 Cryo-EM structures reveal the PP2A-B55α and Eya3 interaction that can be disrupted by a peptide inhibitor. bioRxiv : the preprint server for biology 0 39975004
2025 Cryo-EM structures reveal the PP2A-B55α and Eya3 interaction that can be disrupted by a peptide inhibitor. The Journal of biological chemistry 0 40414499
2025 PR55α subunit of protein phosphatase 2A supports KRASG12D-driven tumorigenesis that requires YAP activation. Oncogene 0 40571777
2024 PPP2R2A promotes Hu sheep pituitary cell proliferation and gonadotropin secretion associated with prolificacy. Animal reproduction science 0 38677100
2024 Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia. Journal of translational medicine 0 39506809

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