Affinage

PPP2CA

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform · UniProt P67775

Round 2 corrected
Length
309 aa
Mass
35.6 kDa
Annotated
2026-04-28
130 papers in source corpus 47 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP2CA encodes the α isoform of the catalytic subunit of protein phosphatase 2A (PP2A), a metal-dependent serine/threonine phosphatase that functions within heterotrimeric holoenzymes whose substrate specificity is dictated by variable regulatory B subunits and whose activity is regulated by reversible Leu309 carboxylmethylation (controlling B55 subunit recruitment), CDK1-mediated threonine phosphorylation (disrupting B55 assembly to promote mitotic entry), PKC-mediated Ser24 phosphorylation (coupling to IGBP1 to trigger AKT inactivation and apoptosis), and ubiquitin-dependent degradation by E3 ligases including MID1, gp78, and MKRN2 (PMID:10446173, PMID:32900880, PMID:38419089, PMID:25207814, PMID:39297166, PMID:40959281). PP2A-PPP2CA dephosphorylates a broad substrate repertoire—including tau, cohesin, MEK/ERK, MST1/2, ULK1-Ser637, DCK-Ser74, c-Myc-Ser62, and CaMKIIα—thereby regulating processes spanning cell cycle progression, centromeric cohesion protection, autophagy, DNA methylation, innate immune signaling (cGAS-STING), and neurodegeneration (PMID:16262633, PMID:16541025, PMID:23775084, PMID:36757811, PMID:39041921, PMID:37437018, PMID:17632056, PMID:16516168). Global phosphoproteomics following selective PPP2CA degradation identified over 2,200 pSP/pTP-containing substrates implicating it in spliceosome function, RNA transport, and ubiquitin-mediated proteolysis (PMID:38450154). De novo PPP2CA mutations cause syndromic intellectual disability through diverse mechanisms including haploinsufficiency, impaired catalytic activity, and dominant-negative disruption of holoenzyme assembly (PMID:30595372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    The functional conservation and modular architecture of PP2Ac was established: human PP2Ac complements yeast PP2A, its C-terminal Leu309 is dispensable for catalysis but required for B55 subunit binding, and truncated/active-site mutants exert dominant-negative effects by titrating regulatory subunits.

    Evidence Yeast complementation with human PP2Ac and mutagenesis of active-site and C-terminal residues

    PMID:10446173

    Open questions at the time
    • Structural basis for Leu309-dependent B55 recruitment was unknown
    • Whether methylation at Leu309 is the regulatory event was not demonstrated in this system
  2. 2000 High

    The selectivity of C-terminal leucine methylation for B-subunit classes was resolved: mutation of the equivalent yeast residue abolished B55/Cdc55p but not B'/Rts1p binding, linking methylation to spindle checkpoint function.

    Evidence Yeast genetics with Leu377 mutation and microtubule destabilization sensitivity assay

    PMID:11129046

    Open questions at the time
    • The methyltransferase and demethylase were not yet identified in this system
    • Whether this selectivity applies in mammalian cells was untested
  3. 2003 High

    The catalytic mechanism of the PP2C-type phosphatase domain was elucidated, identifying essential metal-coordinating residues (Asp60, Asp239, Asp282) and a general acid (His62), with a third Mg²⁺ ion later shown to be required for substrate hydrolysis.

    Evidence Site-directed mutagenesis with kinetic analysis, isothermal titration calorimetry, and Brønsted analysis

    PMID:12859198 PMID:23906386 PMID:25708299

    Open questions at the time
    • Note: these mechanistic studies were performed on PP2Cα/PPM1A, not PPP2CA; cross-family extrapolation should be made cautiously
    • Transition-state structure not resolved
  4. 2005 High

    Two key substrate relationships were established: PP2A accounts for ~71% of tau phosphatase activity in human brain (decreased in Alzheimer disease), and PP2Ac associates with p70S6K within the mTOR pathway where FRAP/mTOR restrains PP2A activity.

    Evidence In vitro dephosphorylation assays with purified phosphatases and hyperphosphorylated tau; co-IP of PP2A with p70S6K and in vitro kinase/phosphatase assays with rapamycin

    PMID:10200280 PMID:16262633

    Open questions at the time
    • Which PP2A holoenzyme dephosphorylates tau in vivo was undefined
    • Whether mTOR directly phosphorylates PP2Ac or the A/B subunits was unresolved
  5. 2006 High

    Shugoshin was identified as the recruiter of a specific PP2A holoenzyme to centromeres, where PP2A dephosphorylates cohesin to protect it from premature dissolution during mitosis and meiosis.

    Evidence Co-purification of PP2A with shugoshin, in vitro cohesin dephosphorylation, centromeric co-localization, and fission yeast genetic validation

    PMID:16541025

    Open questions at the time
    • The specific B-subunit isoform mediating centromeric recruitment was not fully defined
    • Structural basis of shugoshin–PP2A interaction was not resolved
  6. 2007 High

    CIP2A was identified as a direct PP2Ac-binding oncoprotein that inhibits PP2A activity toward c-Myc Ser62, stabilizing c-Myc and promoting transformation, while PP2Cα knockdown separately revealed roles in G1 checkpoint and tumor suppression.

    Evidence Co-IP, in vitro PP2A activity assays with c-Myc substrate, soft agar and xenograft assays; siRNA knockdown cell-cycle analysis

    PMID:17632056 PMID:17941990

    Open questions at the time
    • Whether CIP2A targets a specific holoenzyme or free PP2Ac was unclear
    • Mechanisms linking PP2Cα to cell cycle checkpoint were not defined at substrate level
  7. 2011 High

    The essential, non-redundant role of Ppp2ca in mammalian development was established: homozygous Ppp2ca knockout causes embryonic lethality at ~E6.5, while Ppp2cb deletion has no obvious phenotype.

    Evidence Cre-loxP conditional knockout mice with embryonic lethality assessment

    PMID:21998041

    Open questions at the time
    • The specific PP2A substrates whose dysregulation causes lethality were unknown
    • Tissue-specific requirements beyond early embryogenesis were only beginning to be explored
  8. 2013 High

    PP2Ac was positioned as a regulator of DNA methylation in T cells: it dephosphorylates MEK/ERK upstream of DNMT1, and its overexpression in SLE T cells contributes to DNA hypomethylation of methylation-sensitive genes.

    Evidence siRNA and chemical inhibition with phosphorylation and DNMT activity readouts, validated in SLE patient T cells

    PMID:23775084

    Open questions at the time
    • Which PP2A holoenzyme targets MEK/ERK in T cells was unresolved
    • Causal contribution of PP2Ac overexpression to SLE pathogenesis was correlative
  9. 2016 Medium

    Multiple regulatory inputs onto PP2Ac were delineated: Gi-coupled receptor signaling drives Leu309 carboxylmethylation via PI3K/LCMT-1 and subcellular translocation; GSK-3β controls PP2Ac activation to dephosphorylate IKK/IκBα; and PP2Ac expression level determines differential routing of p38-TSC-mTORC1 signaling.

    Evidence Subcellular fractionation, co-IP of PP2Ac-LCMT-1, PI3K inhibitor studies, siRNA/OA epistasis, phospho-TSC2 site-specific proteomics, PDX tumor models

    PMID:24475092 PMID:26844273 PMID:27851811

    Open questions at the time
    • Whether methylation-dependent translocation occurs in non-cardiac tissues was untested
    • Quantitative relationship between PP2Ac expression and mTORC1 routing was not modeled
  10. 2017 High

    Structural understanding of PP2A regulation advanced: the TIPRL crystal structure revealed it blocks the PP2Ac active site via C-terminal tail binding, while HDX-MS showed the third Mg²⁺ ion rigidifies the PP2Cα active site and Flap subdomain.

    Evidence X-ray crystallography at 2.15 Å, HDX-MS, molecular dynamics simulations, mutagenesis

    PMID:27489114 PMID:28481111

    Open questions at the time
    • Full-length holoenzyme structure with TIPRL was not available
    • Flap subdomain dynamics characterized for PP2Cα may not directly apply to PP2A-type catalytic subunit
  11. 2018 High

    De novo PPP2CA mutations were established as causal for syndromic intellectual disability, with biochemical characterization revealing diverse pathogenic mechanisms including haploinsufficiency, impaired catalysis, altered subunit binding, and dominant-negative effects converging on B56δ dysfunction.

    Evidence Functional characterization of 16 patient variants: phosphatase activity, co-IP for subunit binding, methylation assays, expression analysis

    PMID:30595372

    Open questions at the time
    • Genotype-phenotype correlations for specific variant classes were not fully resolved
    • Whether therapeutic modulation of PP2A could rescue neuronal phenotypes was untested
  12. 2018 High

    PP2Ac Leu309 demethylation was linked to a glucose-sensing cell death pathway: glucose withdrawal triggers membrane depolarization → Cav1.3 Ca²⁺ influx → CAMK1 → PPME1-mediated PP2Ac demethylation → RIPK1 phosphorylation → cell death.

    Evidence Genetic knockdowns of CAMK1 and PPME1, calcium channel inhibition, PP2Ac methylation assays, RIPK1 phosphorylation and viability readouts

    PMID:29317521

    Open questions at the time
    • Which PP2A holoenzyme targets RIPK1 was unknown
    • Whether this pathway operates in non-transformed cells in vivo was not demonstrated
  13. 2019 High

    A widely used PP2Ac post-translational modification — pTyr307 — was shown to be an antibody artifact: commercial antibodies detect Leu309 methylation and Thr304 phosphorylation rather than pTyr307, fundamentally revising interpretation of prior PP2A literature.

    Evidence Targeted mass spectrometry, site-directed mutagenesis of PTM sites, antibody specificity testing, confirmed by two independent labs

    PMID:32130915 PMID:32130916

    Open questions at the time
    • Physiological relevance of authentic pTyr307 remains unclear
    • Many prior studies relying on these antibodies have not been re-evaluated
  14. 2020 High

    A direct CDK1 phosphorylation of PP2Ac was identified that disrupts B55 holoenzyme formation, establishing a direct biochemical mechanism for the CDK1-PP2A antagonism that drives mitotic entry.

    Evidence Chemical proteomics with PPP holoenzyme enrichment, kinase profiling, cell-cycle synchronization

    PMID:32900880

    Open questions at the time
    • The precise threonine residue and its structural impact on B55 binding were not fully characterized
    • Whether this mechanism is conserved across species was untested
  15. 2023 High

    PP2Ac was positioned as a suppressor of innate immune signaling: the PP2Ac/STRN4 holoenzyme dephosphorylates MST1/2 to stabilize YAP/TAZ and antagonize STING, while PP2Ac deficiency in glioma enhanced cGAS-STING and anti-tumor immunity.

    Evidence Macrophage-specific PP2A knockout mouse, co-IP and kinase assays, CRISPR/siRNA in glioma, in vivo tumor models with immune checkpoint blockade, scRNA-seq

    PMID:36757811 PMID:37219874

    Open questions at the time
    • Whether PP2Ac directly dephosphorylates cGAS or STING or acts indirectly via MST1/2 was not resolved
    • Therapeutic window for PP2A inhibition in tumors vs. autoimmune toxicity was not explored
  16. 2023 High

    The global substrate landscape of PPP2CA was mapped: selective dTAG-mediated degradation followed by phosphoproteomics identified >2,200 pSP/pTP substrates implicating PPP2CA in spliceosome function, cell cycle, RNA transport, and ubiquitin-mediated proteolysis.

    Evidence dTAG-selective degradation in knock-in HEK293 cells with unbiased global phosphoproteomics

    PMID:38450154

    Open questions at the time
    • Many identified substrates lack validation as direct PP2A targets
    • Holoenzyme-specific substrate assignments were not made
  17. 2024 High

    Novel regulatory inputs were identified: PKC phosphorylates PP2Ac at Ser24 to initiate the IGBP1-coupled apoptotic switch; S-glutathionylation at Cys314 modulates protein interactions and cell migration; and multiple E3 ligases (gp78, MKRN2) target PP2Ac for ubiquitin-dependent degradation, controlling downstream pathways including DNA damage repair and Wnt signaling.

    Evidence Phospho-mass spectrometry, site-directed mutagenesis (S24A/E, C314), glutathionylation proteomics, ubiquitination assays, in vivo xenograft models

    PMID:38419089 PMID:39297166 PMID:39303918 PMID:40959281

    Open questions at the time
    • Whether Ser24 phosphorylation and Cys314 glutathionylation interact or are mutually exclusive was unknown
    • Relative contribution of individual E3 ligases to steady-state PP2Ac levels in different tissues was not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include which specific holoenzymes mediate each substrate relationship in vivo, how the multiple post-translational modifications on PP2Ac (methylation, phosphorylation at Ser24/Thr304, glutathionylation, ubiquitination) are integrated to determine holoenzyme-specific activity, and whether therapeutic modulation of PP2A can be safely harnessed for cancer immunotherapy and neurodegeneration.
  • Holoenzyme-resolved substrate maps in physiological tissues are lacking
  • Structural basis of Ser24 phosphorylation-induced IGBP1 coupling is unresolved
  • In vivo therapeutic window for PP2A inhibitors in immuno-oncology is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1640170 Cell Cycle 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
CIP2AIGBP1LCMT1MID1PDCD10PPME1PPP2R1ATIPRL
Complex memberships
PP2A holoenzyme (A-B-C trimer)PP2Ac-STRN4 complexPP2Ac-alpha4 complexPP2Ac-shugoshin complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human PP2Ac functionally replaced endogenous PP2Ac in S. cerevisiae, binding the yeast PR65/A subunit (Tpd3p). Truncated or active-site mutant forms of human PP2Ac exerted dominant-negative effects by titrating regulatory subunits/substrates into non-productive complexes. The invariant C-terminal leucine (Leu-309) was found dispensable for activity but required for PR55/B subunit binding. Yeast complementation, mutagenesis, functional phosphatase assays, computer modeling The Journal of biological chemistry High 10446173
2000 Mutation of the C-terminal Leu-377 (equivalent to human Leu-309) of yeast Pph22p abolished binding of the PR55/B subunit Cdc55p but not the PR61/B' subunit Rts1p, and enhanced sensitivity to microtubule destabilization—a spindle checkpoint defect characteristic of cdc55Δ cells—demonstrating that C-terminal leucine methylation regulates B-subunit-specific holoenzyme assembly and spindle checkpoint function. Yeast genetics, in vitro phosphatase assay, microtubule destabilization sensitivity assay Molecular & general genetics : MGG High 11129046
2003 Site-directed mutagenesis of PP2Cα (PPM1A) active site established catalytic roles: Asp-60 (bridges M1/M2) and Asp-239 (coordinates M2) are essential for metal binding and catalysis (>1000-fold decrease in kcat upon mutation); Asp-282 activates a metal-bound water nucleophile; His-62 acts as a general acid during P-O bond cleavage. Site-directed mutagenesis, enzyme kinetic analysis, Brønsted analysis Biochemistry High 12859198
2003 Purified PP2Ac interacts with alpha4 protein (a downstream effector of TOR signaling); this interaction was confirmed by GST pulldown and co-immunoprecipitation. PP2A inhibitors okadaic acid and microcystin-LR disrupted the alpha4/PP2Ac complex, suggesting the interaction involves the phosphatase catalytic domain. GST pulldown, co-immunoprecipitation, microcystin-Sepharose affinity purification, phosphatase activity assays Protein expression and purification High 12963337
2006 PP2Ac physically associates with CaMKIIα and alpha4 in brain; neuronal-specific alpha4 knockout impaired learning/memory and elevated CaMKIIα activity in hippocampus. alpha4/PP2Ac complex dephosphorylates CaMKIIα in the cytoplasm (not in PSD), as shown by overexpression studies in neuronal cell lines. Co-immunoprecipitation, neuron-specific Cre knockout mouse, water maze/shuttle-box behavioral assays, CaMKIIα activity assays, alpha4 overexpression Brain research High 16516168
2008 PP2Cα was identified as the major phosphatase activity inhibiting PAK1 in brain extracts; PP2Cα dephosphorylates PAK1 and p38 in the hyperosmotic stress response. PP2Cα knockdown increased p38 activation, while PP2Cα overexpression or its kinase inhibitory domain prevented sorbitol-induced focal adhesion dissolution, placing PP2Cα upstream of PAK1 in the PI3K/PTEN/Cdc42/p38 pathway. Brain extract fractionation, biochemical phosphatase assay, siRNA knockdown, overexpression, RNAi, kinase inhibitor panel, focal adhesion imaging The Journal of biological chemistry High 18586681
2007 PP2Cα knockdown in MCF7 cells reduced the G0/G1 fraction, attenuated G1 checkpoint induction, and increased G2/M and G2 checkpoint; PP2Cα-silenced cells showed increased tumorigenic potential and enhanced in vivo proliferation, indicating a role for PP2Cα in cell cycle regulation and tumor suppression. siRNA knockdown, cell cycle analysis (FACS), clonogenic survival, in vivo xenograft tumor growth Molecular cancer Medium 17941990
2009 LB-100 is a catalytic inhibitor of both PP2Ac (PPP2CA) and PPP5C in vitro; crystal structure of PPP5C co-crystallized with LB-100 at 1.65 Å revealed the 7-oxabicyclo[2.2.1]heptane-2,3-dicarbonyl moiety coordinates with active-site metal ions and key residues conserved in both enzymes. In vitro phosphatase inhibition assays with purified enzymes, X-ray crystallography (1.65 Å), cell-based genetic disruption studies Molecular cancer therapeutics High 30679389
2010 PP2Cα activation (by overexpression or small molecule NPLC0393) terminated TGFβ-Smad3 and TGFβ-p38 signaling in hepatic stellate cells, induced cell cycle arrest, and decreased fibrotic markers in vivo in CCl4- and BDL-induced mouse models. Overexpression, small molecule activation, western blotting, real-time PCR, cell cycle analysis, in vivo mouse fibrosis models PloS one Medium 21151953
2011 Ppp2ca null mutation causes early embryonic lethality at ~E6.5. Conditional null alleles of Ppp2ca and Ppp2cb were generated; global Ppp2ca deletion recapitulated embryonic lethality, while Ppp2cb homozygous deletion showed no obvious morphological/physiological defects, indicating non-redundant essential roles for Ppp2ca in early development. Cre-loxP conditional knockout mouse generation, embryonic lethality assessment, histological analysis Genesis High 21998041
2013 PP2Ac suppresses MEK/ERK phosphorylation in T-cells; chemical or siRNA-mediated suppression of PP2Ac sustained MEK and ERK phosphorylation, increased DNMT1 enzyme activity and DNA hypermethylation. In SLE T-cells, PP2Ac overexpression dephosphorylates MEK/ERK upstream of DNMT1, contributing to DNA hypomethylation and methylation-sensitive gene expression. siRNA knockdown, chemical inhibition, phosphorylation analysis by western blot, DNMT enzyme activity assay, gene expression analysis, phorbol ester/ionomycin stimulation The Journal of biological chemistry High 23775084
2013 Binding of a third Mg2+ ion to a low-affinity site (coordinated by Asp239 and Asp146/Asp243) in PP2Cα is required for phosphatase activity toward phosphopeptide substrates; isothermal titration calorimetry distinguished two high-affinity sites from a third millimolar-affinity site, and mutational analysis confirmed both Asp146 and Asp239 are required for catalysis. Isothermal titration calorimetry, site-directed mutagenesis, phosphatase activity assays, mixed metal ion experiments Biochemistry High 23906386
2014 PPP2CA restoration in prostate cancer cells decreased nuclear accumulation and transcriptional activity of β-catenin/NF-κB via Akt-mediated GSK3β inactivation and IκB-α inactivation, reversed EMT, and suppressed tumor growth and metastasis in an orthotopic mouse model. Stable transfection, western blot, immunofluorescence, luciferase reporter assay, orthotopic mouse model, immunohistochemistry British journal of cancer Medium 24642616
2014 MID1 E3 ubiquitin ligase catalyzes in vitro ubiquitination of PP2Ac directly (in absence of alpha4); alpha4 reduces PP2Ac ubiquitination level. Bbox1 domain mutations associated with X-linked Opitz G syndrome abrogate alpha4 but not PP2Ac polyubiquitination by MID1. In vitro ubiquitination assay, co-immunoprecipitation, transfection with deletion constructs PloS one Medium 25207814
2015 Ppp2ca conditional knockout in male mouse germ cells caused infertility; exon 2 deletion in primordial germ cells resulted in spermatogenesis failure, demonstrating an essential role of Ppp2ca in male germ cell development. Conditional knockout mouse (Cre-loxP, primordial germ cell-specific Cre at E12.5), fertility testing, histological analysis Reproduction Medium 25628439
2015 Mutation of structurally buried D38 in PP2Cα selectively disrupts M2 metal ion binding by redefining the water-mediated hydrogen network in the active site; D38A and D38K mutants demonstrated that M2 determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding, and stabilizes the leaving group after P-O bond cleavage. Site-directed mutagenesis, enzymology analysis, X-ray-informed structural analysis Scientific reports High 25708299
2016 PP2Acα regulates hair follicle morphogenesis and the hair regeneration cycle; epidermal-specific Ppp2ca knockout (Krt14-Cre) caused hair loss, disrupted hair follicle morphogenesis, melanin deposition and hyperproliferation at claw base. Conditional knockout (Krt14-Cre), histological analysis, phenotypic characterization International journal of molecular sciences Medium 27213341
2016 PP2Ac (PP2Cα) dephosphorylates PAK1 and p38 in brain; in endothelial cells, PP2Ac-dependent activation of Raf-MEK-ERK signaling was required for TGF-β1-induced glutaminolysis. Inhibition of PP2Ac by okadaic acid or PP2Ac depletion abolished Raf-MEK-ERK activation and reduced KGA expression and glutamine metabolism. siRNA depletion, okadaic acid inhibition, western blotting, glutamate level measurement, MEK inhibitor U0126 experiments PloS one Medium 27612201
2016 In cardiomyocytes, Gi-coupled receptor (A1R, M2R, AT2R) stimulation induces PP2Ac carboxylmethylation at Leu309 via a GiPCR-Gβγ-PI3K pathway, and this correlates with PP2Ac translocation to the particulate fraction. LCMT-1 interaction with PP2Ac increased after A1R stimulation; PI3K inhibitor LY294002 abrogated both methylation-dependent translocation effects. Western blot for methylated PP2Ac, subcellular fractionation, adenoviral Gαt1 expression, PI3K inhibitor, co-immunoprecipitation of PP2Ac-LCMT-1 PloS one Medium 24475092
2016 Melatonin (via MT2 receptor) increases PP2Ac expression in spinal dorsal horn; PP2Ac dephosphorylates HDAC4, promoting HDAC4 nuclear accumulation which suppresses hmgb1 transcription, thereby relieving neuropathic allodynia. Spinal PP2Ac knockdown alone caused allodynia and mimicked SNL-induced changes. siRNA knockdown, intrathecal drug administration, western blot, immunofluorescence, behavioral pain testing, MT2 antagonist Journal of pineal research Medium 26732138
2016 GSK-3β activation leads to PP2Ac dephosphorylation/activation in cardiomyocytes; activated PP2Ac dephosphorylates IKK/IκBα, reducing NF-κB nuclear translocation and apoptosis. Atorvastatin protects cardiomyocytes from high glucose-induced apoptosis by inactivating GSK-3β and activating PP2Ac, an effect abolished by PP2Ac siRNA or okadaic acid. siRNA, okadaic acid inhibition, western blot (phospho-GSK3β, phospho-PP2Ac, phospho-IKK, NF-κB translocation), in vivo diabetic mouse model PloS one Medium 27851811
2016 PP2Ac expression level determines differential routing of p38-TSC-mTORC1 signaling by controlling TSC2 phosphorylation at S664, S1254, and S1798 in colorectal cancer. Modulation of PP2Ac level was sufficient to reprogram p38-to-mTORC1 signaling and antitumor response to p38 inhibitors. PP2Ac overexpression/knockdown, phospho-proteomics (TSC2 site-specific), cell line and PDX tumor models, p38 inhibitor treatment EBioMedicine Medium 26844273
2017 Crystal structure of human TIPRL solved at 2.15 Å; TIPRL binds the conserved C-terminal tail of PP2Ac via a conserved cleft, preferentially binding unmodified (vs. Tyr-phosphorylated) tail peptide DYFL. Mutagenesis, pulldown, and hydrogen/deuterium exchange MS showed TIPRL blocks the PP2Ac active site, providing structural basis for PP2A inhibition. X-ray crystallography (2.15 Å), site-directed mutagenesis, GST pulldown, hydrogen/deuterium exchange mass spectrometry, docking model Scientific reports High 27489114
2017 DDX3 forms a complex with PP2Ac and IKK-β (identified by co-IP and mass spectrometry); DDX3 regulates PP2Ac phosphorylation, which modulates NF-κB signaling by controlling IKK-β dephosphorylation. DDX3 knockdown reduced p65 and IKK-β phosphorylation and attenuated inflammatory cytokine production. Co-immunoprecipitation, mass spectrometry, siRNA knockdown, western blot, cytokine ELISA Oncotarget Medium 28402257
2017 H/D exchange-MS and molecular dynamics revealed that binding of the third Mg2+ ion to the D146/D239 site rigidifies the active site and Flap subdomain of PP2Cα; the D146A mutation increases conformational mobility in the Flap subdomain, and the presence of the third metal ion is distinct from the D146A mutant in producing conformational realignments. Hydrogen/deuterium exchange mass spectrometry, molecular dynamics simulations Biochemistry High 28481111
2018 De novo mutations in PPP2CA cause syndromic intellectual disability. Functional studies showed diverse mechanisms: haploinsufficiency (4 individuals), complete PP2A dysfunction; 10 others showed poor expression, altered A-subunit binding, impaired phosphatase activity, impaired C-terminal methylation, or altered B-subunit binding; 4 dominant-negative. All pathogenic variants impaired PP2A-B56δ functionality. Biochemical characterization of patient-derived mutations: phosphatase activity assay, co-immunoprecipitation for subunit binding, methylation assays, expression analysis American journal of human genetics High 30595372
2018 Glucose withdrawal triggers PP2Ac demethylation via a pathway involving plasma membrane depolarization → Cav1.3 Ca2+ influx → CAMK1 activation → PPME1-mediated PP2Ac demethylation → RIPK1 phosphorylation → cell death. Glucose (and non-metabolizable 2-DG) prevented PP2Ac demethylation and cell death, revealing glucose as a signaling molecule protecting from membrane depolarization-induced death. Sibling knockdowns (CAMK1, PPME1), calcium channel inhibition, L-type channel blockade, PP2Ac methylation western blot, RIPK1 phosphorylation, cell viability assays Science signaling High 29317521
2019 PP2Ac phosphorylation at Tyr307 previously attributed to PP2Ac inactivation is not reliably detected by commercial antibodies (E155, F-8); these antibodies are sensitive to Leu309 methylation and Thr304 phosphorylation rather than pTyr307. Targeted mass spectrometry identified pTyr307 only upon overexpression of PP2Ac with Src kinase, but none of the antibodies showed exclusive specificity under these conditions. Targeted mass spectrometry, antibody specificity testing, site-directed mutagenesis of PTM sites, overexpression of Src kinase Cell reports High 32130915 32130916
2020 CDK1 directly phosphorylates a threonine residue on PP2Ac, disrupting its holoenzyme formation with the B55 regulatory subunit. This decreases dephosphorylation of PP2A-B55 substrates and promotes mitotic entry, adding a direct phosphorylation layer to the known indirect CDK1-PP2A interaction in cell cycle control. Mass spectrometry-based chemical proteomics (PPP holoenzyme enrichment), kinase profiling, cell cycle synchronization, phosphorylation site validation Science signaling High 32900880
2021 PP2Ac methylation (via SAM/LCMT-1) is necessary for M1 macrophage polarization, positively regulating VDAC1 and PINK1 to promote mitophagy-dependent metabolic switch to glycolysis. Taurine inhibits SAM-dependent PP2Ac methylation, blocking PINK1-mediated mitophagy flux and thereby preventing the glycolytic switch required for M1 polarization. SAM quantification, LCMT-1/PME-1 activity assays, PP2Ac methylation assay, mitophagy flux measurement, metabolic assays, siRNA knockdown Frontiers in immunology Medium 33912173
2021 PDCD10 directly binds PP2Ac and increases its enzymatic activity, leading to YAP dephosphorylation, YAP nuclear translocation, and transcriptional activation promoting HCC metastasis and EMT. Knockdown of PP2Ac abolished PDCD10-mediated HCC progression. Co-immunoprecipitation, phosphatase activity assay, siRNA knockdown, in vitro migration/invasion assays, in vivo xenograft Cell death & disease Medium 34521817
2023 PP2Ac/STRN4 holoenzyme negatively regulates STING-type I IFN signaling in macrophages by binding and dephosphorylating Hippo kinase MST1/2, stabilizing YAP/TAZ to antagonize STING activation. STING agonists induced dissociation of PP2Ac from MST1/2 in normal but not tumor-conditioned macrophages. Macrophage-specific PP2A knockout mouse, co-immunoprecipitation, kinase activity assay, STING agonist treatment, single-cell transcriptomics, tumor models The Journal of clinical investigation High 36757811
2023 PP2Ac deficiency in glioma cells enhanced dsDNA production and cGAS-type I IFN signaling, increased MHC-I expression and tumor mutational burden. In co-culture, PP2Ac-deficient glioma cells promoted DC cross-presentation and CD8+ T cell clonal expansion; in vivo PP2Ac depletion sensitized tumors to immune-checkpoint blockade. Genetic ablation (CRISPR/siRNA), cGAS-STING signaling assays, MHC-I flow cytometry, DC/T-cell co-culture, in vivo tumor models, single-cell RNA-seq Cancer research High 37219874
2023 Global phospho-proteomics using dTAG-mediated selective degradation of PPP2CA identified 2,204 proteins with increased phosphorylation as potential PPP2CA substrates; predominant motif is pSP/pTP. Substrates implicate PPP2CA in spliceosome function, cell cycle, RNA transport, and ubiquitin-mediated proteolysis. dTAG proteolysis-targeting chimera degradation of endogenous PPP2CA in knock-in HEK293 cells, unbiased global phospho-proteomics, immunoblotting validation iScience High 38450154
2023 PTEN directly binds and dephosphorylates the C-terminus of PP2Ac to increase its enzymatic activity; activated PP2Ac then dephosphorylates deoxycytidine kinase (DCK) at Ser74, reducing DCK activity and diminishing gemcitabine efficacy. PTEN deficiency increases PP2Ac C-terminal phosphorylation, reducing its activity and boosting DCK-Ser74 phosphorylation. Cell-based drug sensitivity assays, in vitro binding and phosphatase assays, cell line-derived and PDX xenograft models Science translational medicine High 37437018
2024 PKC (classical isoforms PKCα and PKCβ) phosphorylates PP2Ac at Ser24, and this phosphorylation initiates the PP2A switch (coupling to IGBP1) that induces AKT inactivation and JNK-dependent apoptosis upon GqPCR activation. S24A (unphosphorylatable) and S24E (phosphomimetic) mutations confirmed Ser24 phosphorylation is necessary and sufficient for the PP2A switch. Phospho-mass spectrometry to identify Ser24, site-directed mutagenesis (S24A/S24E), co-immunoprecipitation, proximity ligation assay, TUNEL/PARP1 cleavage apoptosis assays Cell communication and signaling High 38419089
2024 PP2Cα is susceptible to S-glutathionylation selectively at non-conserved Cys314; glutathionylation modulates PP2Cα protein-protein interactions and activates JNK and ERK pathways, increasing breast cancer cell migration and invasion in response to oxidative stress or EGF. Glutathionylation proteomics, site-directed mutagenesis (C314), cell migration/invasion assays, H2O2 and EGF treatment, JNK/ERK phosphorylation assays The Journal of biological chemistry Medium 39303918
2024 gp78 E3 ligase promotes ubiquitination-dependent degradation of PP2Ac (and PP1CC), thereby elevating KAP1 phosphorylation and promoting DNA damage repair and radioresistance in breast cancer cells. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, western blot for phospho-KAP1, clonogenic survival post-irradiation iScience Medium 39297166
2024 PP2Ac regulates autophagy during osteoclastogenesis by dephosphorylating ULK1 at Ser637, which is required for ULK1-dependent autophagy initiation; mTORC1 inhibition upregulates PP2Ac expression, linking mTORC1-PP2Ac-ULK1 in osteoclast autophagy regulation. PP2Ac knockdown/inhibition, ULK1 phosphorylation assays, autophagy flux measurement, mTORC1 inhibitor experiments, OA mouse model Advanced science Medium 39041921
2025 MKRN2 E3 ligase interacts with PPP2CA and promotes K48-linked ubiquitination at K41, leading to proteasomal degradation of PPP2CA; this increases β-catenin phosphorylation and decreases β-catenin protein levels, inactivating Wnt signaling in clear cell renal cell carcinoma. Co-immunoprecipitation, immunofluorescence, western blot, K48-ubiquitination assay, β-catenin phosphorylation assay, in vivo xenograft International journal of biological sciences Medium 40959281
2025 PP2Ac carboxy-methylation (at Leu309 via SAM/LCMT-1) is highly sensitive to intracellular SAM levels; reduced methylation correlates with impaired cancer cell proliferation under methionine restriction. PME-1 overexpression (demethylating PP2Ac) or a Leu309-deleted PP2Ac mutant reduced proliferation even in methionine-independent cells, linking methionine metabolism to cell proliferation via PP2Ac methylation status. PP2Ac methylation analysis, PME-1 overexpression, Leu309-deleted mutant expression, cell proliferation assays under methionine restriction Biomolecules Medium 41008516
2005 PP2Ac (PP2A catalytic subunit) associates with p70 S6 kinase (p70s6k); FRAP/mTOR phosphorylates PP2A in vitro, and PP2A activity toward 4E-BP1 increases upon rapamycin treatment, suggesting FRAP restrains PP2A to maintain p70s6k and 4E-BP1 phosphorylation in the mTOR pathway. Co-immunoprecipitation (PP2A with p70s6k), in vitro kinase assay (FRAP phosphorylates PP2A), PP2A activity assay after rapamycin treatment Proceedings of the National Academy of Sciences of the United States of America High 10200280
2006 Shugoshin recruits a specific PP2A holoenzyme to centromeres; this centromeric PP2A dephosphorylates cohesin, protecting it from mitotic dissolution. Purified shugoshin complex reversed cohesin phosphorylation in vitro; meiotic shugoshin of fission yeast similarly associates with PP2A to protect Rec8 cohesin. Co-purification of PP2A with shugoshin, in vitro dephosphorylation of cohesin by shugoshin-PP2A complex, shugoshin/PP2A co-localization at centromeres, fission yeast genetics Nature High 16541025
2005 PP2A dephosphorylates tau at multiple sites (Ser199, Ser202, Thr205, Thr212, Ser214, Ser235, Ser262, Ser396, Ser404, Ser409) and accounts for ~71% of total tau phosphatase activity in human brain; PP2A activity negatively correlates with tau phosphorylation levels at most sites in human brain, and PP2A activity toward tau is decreased in Alzheimer disease brain. In vitro dephosphorylation assays with purified PP1, PP2A, PP2B, PP5 and hyperphosphorylated tau; Km determination; quantification of phosphatase activities in human brain extracts; comparison of AD vs. control brain The European journal of neuroscience High 16262633 7616230
2007 CIP2A directly interacts with PP2Ac and inhibits PP2A activity toward c-Myc Ser62, preventing c-Myc proteolytic degradation. CIP2A overexpression promotes anchorage-independent cell growth and in vivo tumor formation; knockdown reduces c-Myc levels. Co-immunoprecipitation, in vitro PP2A activity assay with c-Myc as substrate, overexpression/knockdown, soft agar growth, in vivo tumor formation Cell High 17632056

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2017 Roles of tau protein in health and disease. Acta neuropathologica 716 28386764
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 An empirical framework for binary interactome mapping. Nature methods 652 19060904
1995 Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature 632 8524402
2005 Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. The European journal of neuroscience 617 16262633
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
2007 CIP2A inhibits PP2A in human malignancies. Cell 535 17632056
1989 Protein phosphatases come of age. The Journal of biological chemistry 530 2557326
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
2006 Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 480 16541025
1999 Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. The EMBO journal 475 10357815
2005 Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 443 16239144
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1999 Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein. Proceedings of the National Academy of Sciences of the United States of America 422 10200280
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1995 Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain. Journal of neurochemistry 396 7616230
2013 The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway in T-cells from controls and systemic lupus erythematosus patients. The Journal of biological chemistry 85 23775084
2014 Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients. Lupus 64 25253569
1999 Functional expression of human PP2Ac in yeast permits the identification of novel C-terminal and dominant-negative mutant forms. The Journal of biological chemistry 62 10446173
2003 Probing the function of conserved residues in the serine/threonine phosphatase PP2Calpha. Biochemistry 60 12859198
2003 Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein. Protein expression and purification 60 12963337
2021 Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation. Frontiers in immunology 57 33912173
2014 Restoration of PPP2CA expression reverses epithelial-to-mesenchymal transition and suppresses prostate tumour growth and metastasis in an orthotopic mouse model. British journal of cancer 48 24642616
2008 PAK is regulated by PI3K, PIX, CDC42, and PP2Calpha and mediates focal adhesion turnover in the hyperosmotic stress-induced p38 pathway. The Journal of biological chemistry 48 18586681
2019 The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C. Molecular cancer therapeutics 47 30679389
2004 PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers. Oncology reports 47 14767517
2011 Generation of Ppp2Ca and Ppp2Cb conditional null alleles in mouse. Genesis (New York, N.Y. : 2000) 46 21998041
2018 De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders. American journal of human genetics 45 30595372
2016 Melatonin relieves neuropathic allodynia through spinal MT2-enhanced PP2Ac and downstream HDAC4 shuttling-dependent epigenetic modification of hmgb1 transcription. Journal of pineal research 42 26732138
2000 Mutation of the C-terminal leucine residue of PP2Ac inhibits PR55/B subunit binding and confers supersensitivity to microtubule destabilization in Saccharomyces cerevisiae. Molecular & general genetics : MGG 40 11129046
2023 PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma. Cancer research 39 37219874
2011 Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. Arthritis and rheumatism 36 21590681
2023 PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages. The Journal of clinical investigation 34 36757811
2006 Regulation of CaMKII by alpha4/PP2Ac contributes to learning and memory. Brain research 32 16516168
2017 (DEAD)-box RNA helicase 3 modulates NF-κB signal pathway by controlling the phosphorylation of PP2A-C subunit. Oncotarget 30 28402257
2016 Atorvastatin Alleviates Experimental Diabetic Cardiomyopathy by Regulating the GSK-3β-PP2Ac-NF-κB Signaling Axis. PloS one 30 27851811
2015 Ppp2ca knockout in mice spermatogenesis. Reproduction (Cambridge, England) 30 25628439
2019 miR-650 promotes motility of anaplastic thyroid cancer cells by targeting PPP2CA. Endocrine 29 30927143
2013 Binding of a third metal ion by the human phosphatases PP2Cα and Wip1 is required for phosphatase activity. Biochemistry 29 23906386
2007 Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity. Molecular cancer 29 17941990
2015 The catalytic role of the M2 metal ion in PP2Cα. Scientific reports 26 25708299
2010 Activation of protein serine/threonine phosphatase PP2Cα efficiently prevents liver fibrosis. PloS one 26 21151953
2021 Tumor-associated macrophages promote the metastasis and growth of non-small-cell lung cancer cells through NF-κB/PP2Ac-positive feedback loop. Cancer science 24 33609307
2021 Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation. Cell death & disease 24 34521817
2016 Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac. Cell cycle (Georgetown, Tex.) 24 26761431
2015 PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine 24 26844273
2023 ALA reverses ABA-induced stomatal closure by modulating PP2AC and SnRK2.6 activity in apple leaves. Horticulture research 22 37287446
2018 Ca2+-dependent demethylation of phosphatase PP2Ac promotes glucose deprivation-induced cell death independently of inhibiting glycolysis. Science signaling 22 29317521
2016 Glutaminolysis Was Induced by TGF-β1 through PP2Ac Regulated Raf-MEK-ERK Signaling in Endothelial Cells. PloS one 22 27612201
2011 PPM-1, a PP2Cα/β phosphatase, regulates axon termination and synapse formation in Caenorhabditis elegans. Genetics 22 21968191
2023 YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification. Biological procedures online 21 36870954
2023 Luteolin directly binds to KDM4C and attenuates ovarian cancer stemness via epigenetic suppression of PPP2CA/YAP axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 36804120
2020 PP2AC Phospho-Tyr307 Antibodies Are Not Specific for this Modification but Are Sensitive to Other PP2AC Modifications Including Leu309 Methylation. Cell reports 19 32130916
2020 Quantitative kinase and phosphatase profiling reveal that CDK1 phosphorylates PP2Ac to promote mitotic entry. Science signaling 19 32900880
2023 PTEN deficiency facilitates gemcitabine efficacy in cancer by modulating the phosphorylation of PP2Ac and DCK. Science translational medicine 18 37437018
2020 Challenges and Reinterpretation of Antibody-Based Research on Phosphorylation of Tyr307 on PP2Ac. Cell reports 17 32130915
2014 MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PloS one 16 25207814
2022 The miR-345-3p/PPP2CA signaling axis promotes proliferation and invasion of breast cancer cells. Carcinogenesis 15 34922339
2016 Conditional Knockout in Mice Reveals the Critical Roles of Ppp2ca in Epidermis Development. International journal of molecular sciences 15 27213341
2016 Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus. Scientific reports 15 27489114
2024 Mapping the substrate landscape of protein phosphatase 2A catalytic subunit PPP2CA. iScience 14 38450154
2024 Drug-resistant exosome miR-99b-3p induces macrophage polarization and confers chemoresistance on sensitive cells by targeting PPP2CA. International immunopharmacology 14 39298813
2020 Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 14 32959271
2015 Norcantharidin inhibits renal interstitial fibrosis by downregulating PP2Ac expression. American journal of translational research 14 26807168
2023 Low-dose benzo[a]pyrene exposure induces hepatic lipid deposition through LCMT1/PP2Ac-mediated autophagy inhibition. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 13 37579989
2013 Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac. Molecular and cellular endocrinology 13 24145130
2010 Synthesis of C-glycoside analogues of beta-galactosamine-(1-->4)-3-O-methyl-D-chiro-inositol and assay as activator of protein phosphatases PDHP and PP2Calpha. Bioorganic & medicinal chemistry 13 20079654
2019 PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death. Apoptosis : an international journal on programmed cell death 12 31605257
2014 Regulation of PP2AC carboxylmethylation and cellular localisation by inhibitory class G-protein coupled receptors in cardiomyocytes. PloS one 12 24475092
2022 KHSRP modulated cell proliferation and cell cycle via regulating PPP2CA and p27 expression in Wilms tumor. Cellular signalling 11 36029941
2021 Regulation PP2Ac methylation ameliorating autophagy dysfunction caused by Mn is associated with mTORC1/ULK1 pathway. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 11 34363881
2021 Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma. Journal of clinical and translational hepatology 11 34722181
2016 The three Type 2A protein phosphatases, PP2Ac, PP4c and PP6c, are differentially regulated by Alpha4. Biochemical and biophysical research communications 11 27169767
2015 Systematic study of cis-antisense miRNAs in animal species reveals miR-3661 to target PPP2CA in human cells. RNA (New York, N.Y.) 11 26577378
2017 Genetic variants in PPP2CA are associated with gastric cancer risk in a Chinese population. Scientific reports 9 28904398
2013 GADD45α induction by nickel negatively regulates JNKs/p38 activation via promoting PP2Cα expression. PloS one 9 23536762
2024 Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis. Cell communication and signaling : CCS 8 38419089
2024 PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer. Digestive diseases and sciences 8 38637456
2022 PPP2CA Is a Novel Therapeutic Target in Neuroblastoma Cells That Can Be Activated by the SET Inhibitor OP449. Frontiers in oncology 8 35814385
2007 Depletion of the catalytic subunit of protein phosphatase-2A (PP2Ac) markedly attenuates glucose-stimulated insulin secretion in pancreatic beta-cells. Endocrine 8 17906371
2005 The heterodimer of alpha4 and PP2Ac is associated with S6 kinase1 in B cells. Biochemical and biophysical research communications 8 15796902
2024 PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39041921
2021 PP2A-C may be a promising candidate for postmortem interval estimation. International journal of legal medicine 7 33409557
2017 Conformational Changes in Active and Inactive States of Human PP2Cα Characterized by Hydrogen/Deuterium Exchange-Mass Spectrometry. Biochemistry 7 28481111
2024 Protein phosphatase PP2Cα S-glutathionylation regulates cell migration. The Journal of biological chemistry 6 39303918
2023 Metformin alleviates lung-endothelial hyperpermeability by regulating cofilin-1/PP2AC pathway. Frontiers in pharmacology 6 37361221
2020 Reduced methylation of PP2Ac promotes ethanol-induced lipid accumulation through FOXO1 phosphorylation in vitro and in vivo. Toxicology letters 6 32492475
2020 Anti-renal interstitial fibrosis effect of norcantharidin is exerted through inhibition of PP2Ac-mediated C-terminal phosphorylation of Smad3. Chemical biology & drug design 6 32896083
2019 PP2Ac Modulates AMPK-Mediated Induction of Autophagy in Mycobacterium bovis-Infected Macrophages. International journal of molecular sciences 6 31795474
2024 TaNAC1 boosts powdery mildew resistance by phosphorylation-dependent regulation of TaSec1a and TaCAMTA4 via PP2Ac/CDPK20. The New phytologist 5 39183373
2024 Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA. International journal of nanomedicine 5 39253060
2023 Volatile oil of Angelica sinensis Radix improves cognitive function by inhibiting miR-301a-3p targeting Ppp2ca in cerebral ischemia mice. Journal of ethnopharmacology 5 38154524
2022 Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Influences the Meiosis Initiation During Spermatocyte Meiosis Prophase I. Reproductive sciences (Thousand Oaks, Calif.) 5 35041133
2022 PP2Cα positively regulates neuronal insulin signalling and aggravates neuronal insulin resistance. The FEBS journal 5 35810470
2022 Clinical and molecular characteristics of a novel rare de novo variant in PPP2CA in a patient with a developmental disorder, autism, and epilepsy. Frontiers in cell and developmental biology 5 36531959
2018 Association between PPP2CA polymorphisms and clinical features in southwest Chinese systemic lupus erythematosus patients. Medicine 5 29979448
2024 gp78-regulated KAP1 phosphorylation induces radioresistance in breast cancer by facilitating PPP1CC/PPP2CA ubiquitination. iScience 4 39297166
2023 PP2Cα aggravates neuronal insulin resistance leading to AD-like phenotype in vitro. Biochemical and biophysical research communications 4 36630734
2023 ALA induces stomatal opening through regulation among PTPA, PP2AC, and SnRK2.6. Frontiers in plant science 4 37711306
2022 PP2Acα regulates epidermal cell proliferation via the EGFR/AKT/mTOR pathway in psoriasis-like skin lesions caused by PPP2CA deficiency. Experimental dermatology 4 35298048
2021 TRPC1-mediated Ca2+ signaling enhances intestinal epithelial restitution by increasing α4 association with PP2Ac after wounding. Physiological reports 4 33991460
2025 Colchicine inhibits vascular calcification by suppressing inflammasome activation through the enhancement of the Sirt2-PP2Ac signaling pathway. The Journal of biological chemistry 3 40523615
2025 E3 ligase MKRN2 destabilizes PPP2CA proteins to inactivate canonical Wnt pathway and mitigates tumorigenesis of clear cell renal cell carcinoma. International journal of biological sciences 3 40959281
2025 Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation. Biomolecules 3 41008516
2023 Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 3 38069840
2016 Post-transcriptional modulation of protein phosphatase PPP2CA and tumor suppressor PTEN by endogenous siRNA cleaved from hairpin within PTEN mRNA 3'UTR in human liver cells. Acta pharmacologica Sinica 3 27133296
2025 Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction. Communications biology 2 39838082
2024 Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3β/β-catenin axis. Journal of cancer research and clinical oncology 2 39249161
2023 Quantum-based modeling implies that bidentate Arg89-substrate binding enhances serine/threonine protein phosphatase-2A(PPP2R5D/PPP2R1A/PPP2CA)-mediated dephosphorylation. Frontiers in cell and developmental biology 2 37377738
2025 EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development. Theriogenology 1 40139147
2025 The sperm quality in DIO male mice is linked to the NF-κB signaling and Ppp2ca expression in the hypothalamus. iScience 1 40160428
2025 Triptolide targets PPP2CA/ITGA5 axis to suppress lactate-driven ovarian cancer progression. Chinese medicine 1 40770810
2023 PP2Ac knockdown attenuates lipotoxicity‑induced pancreatic β‑cell dysfunction and apoptosis. Experimental and therapeutic medicine 1 37928506
2025 Mutations Upstream of ppp2ca Affect Body Weight in Asian Seabass. Marine biotechnology (New York, N.Y.) 0 41114894
2025 RCN2 facilitates esophageal squamous cellular carcinoma metastasis and cisplatin resistance through UBR5-mediated PPP2CA ubiquitination and degradation. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 0 41411970
2023 Establishment of a PPP2CA homozygous knockout human embryonic stem cell line via CRISPR/Cas9 system. Stem cell research 0 36724553