Affinage

PPP2CA

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

Length
309 aa
Mass
35.6 kDa
Annotated
2026-06-10
95 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP2CA encodes the catalytic subunit of protein phosphatase 2A (PP2Ac), a serine/threonine phosphatase that dephosphorylates a broad pSP/pTP-motif substrate landscape of >2,000 proteins enriched for cell cycle, RNA processing, and ubiquitin-proteolysis functions to govern proliferation, apoptosis, immune signaling, and cell migration (PMID:38450154, PMID:30595372). PP2Ac assembles with scaffolding (A) and regulatory (B/B'/B''/STRN) subunits into functional holoenzymes; the conserved C-terminal Leu309 region and an intact catalytic core are required for productive B-subunit binding and activity, and active-site or truncation mutants act dominant-negatively by titrating regulatory subunits and substrates (PMID:10446173, PMID:11129046, PMID:36531959). Holoenzyme assembly and activity are tuned by reversible C-terminal carboxylmethylation at Leu309—written by LCMT-1, erased by PME-1, and sensitive to intracellular SAM/methionine availability—which controls B-subunit recruitment, proliferation, and downstream programs (PMID:24475092, PMID:41008516, PMID:32492475); additional post-translational control comes from direct phosphorylation by CDK1, which disrupts PP2A-B55 to promote mitotic entry (PMID:32900880), by classical PKCα/β at Ser24, which triggers an IGBP1/alpha4-dependent switch that inactivates PI3K/AKT and drives JNK-dependent apoptosis (PMID:38419089), and from acetylation at Lys136 controlled by Sirt2 (PMID:40523615). Through defined substrates PP2Ac executes its biology: it dephosphorylates MEK/ERK to suppress the DNMT1 epigenetic axis (PMID:23775084), MST1/2 and YAP to control Hippo signaling, migration and inflammasome output (PMID:34521817, PMID:36757811), RIPK1 in glucose-deprivation cell death (PMID:29317521), IKKβ and p65 in NF-κB signaling (PMID:28402257, PMID:41847846), DCK to modulate gemcitabine sensitivity (PMID:37437018), ULK1 in autophagy (PMID:39041921), and acts via Rho1/RhoA-JNK to drive cell migration (PMID:42144974); it also restrains cGAS-STING type-I interferon responses in tumor cells (PMID:37219874). The alpha4 (IGBP1) chaperone binds PP2Ac through its catalytic domain and protects it from ubiquitin-mediated degradation, while the E3 ligases MID1, EDD, UBR5, and MKRN2 target PP2Ac for proteasomal turnover (PMID:25207814, PMID:24145130, PMID:40959281, PMID:41411970, PMID:12963337). De novo PPP2CA missense and loss-of-function variants cause intellectual disability through haploinsufficient or dominant-negative impairment of phosphatase activity, A/B-subunit binding, and C-terminal methylation (PMID:30595372, PMID:36531959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 High

    Established that human PP2Ac is a functionally conserved catalytic subunit whose activity and proper complex assembly are essential, defining the dominant-negative behavior of catalytically dead forms.

    Evidence Yeast complementation, mutagenesis and in vitro phosphatase assays with active-site and C-terminal mutants

    PMID:10446173

    Open questions at the time
    • Did not map all regulatory subunit contacts in human holoenzymes
    • Leu309 modification chemistry not yet addressed
  2. 2000 High

    Linked the conserved C-terminal leucine to selective B-subunit binding and mitotic checkpoint function, showing modification of this residue differentially gates holoenzyme composition.

    Evidence Yeast genetics, two-hybrid binding, and microtubule-drug phenotyping of Pph22p Leu mutants

    PMID:11129046

    Open questions at the time
    • B-subunit selectivity demonstrated in yeast orthologs, not human subunits directly
    • Methylation status not measured
  3. 2004 Medium

    Defined the region of the scaffolding A subunit required for physical contact with PP2Ac, anchoring the architecture of the core dimer.

    Evidence Co-IP of PPP2R1B deletion/missense mutants from colorectal cancer tissue

    PMID:14767517

    Open questions at the time
    • Single method, no structural validation
    • Functional consequence of disrupted binding not assayed
  4. 2006 High

    Identified the alpha4/PP2Ac complex as a cytoplasmic regulator of CaMKIIα, connecting the phosphatase to learning and memory through compartment-specific substrate dephosphorylation.

    Evidence Neuron-specific alpha4 conditional KO, Co-IP, fractionation and behavioral assays

    PMID:16516168

    Open questions at the time
    • Effects attributed via alpha4 KO rather than direct PP2Ac perturbation
    • Direct CaMKIIα dephosphorylation site not mapped
  5. 2005 Medium

    Mapped distinct binding surfaces on PP2Ac for alpha4 and substrate S6K1, showing alpha4 bridges PP2Ac to substrates under immune stimulation.

    Evidence Pull-down with PP2Ac deletion constructs and LPS-stimulated B cell Co-IP

    PMID:15796902

    Open questions at the time
    • S6K1 dephosphorylation not directly demonstrated
    • Single lab domain mapping
  6. 2013 High

    Placed PP2Ac upstream of the MEK/ERK/DNMT1 axis, defining a route by which the phosphatase controls DNA methylation in T cells.

    Evidence siRNA and chemical inhibition with phospho-ERK, DNMT activity and methylation readouts

    PMID:23775084

    Open questions at the time
    • Direct MEK/ERK dephosphorylation by PP2Ac vs indirect not resolved
    • Relevant holoenzyme/B-subunit unspecified
  7. 2013 High

    Identified MID1, EDD as E3 ligases that ubiquitinate PP2Ac and established alpha4 as a protective chaperone modulating PP2Ac turnover.

    Evidence In vitro ubiquitination, alpha4 deletion-construct Co-IP, siRNA and MG132 treatment

    PMID:24145130 PMID:25207814

    Open questions at the time
    • Ubiquitination site(s) on PP2Ac not mapped in these studies
    • Physiological triggers of degradation partly inferred
  8. 2014 High

    Demonstrated receptor- and PI3K-controlled Leu309 carboxylmethylation governs PP2Ac localization and showed PP2Ac suppresses β-catenin/NF-κB via Akt-GSK3β/IκBα, establishing methylation and signaling control of the phosphatase.

    Evidence Carboxylmethylation assays with Gi-receptor agonists; gain/loss-of-function with reporter and orthotopic models in prostate cancer

    PMID:24475092 PMID:24642616

    Open questions at the time
    • Whether methylation directly dictates specific B-subunit recruitment in these contexts untested
    • Direct substrate of PP2Ac in β-catenin/NF-κB axis not identified
  9. 2016 High

    Provided structural and biochemical basis for C-terminal-tail recognition of PP2Ac by the regulator TIPRL, which preferentially binds unmethylated PP2Ac and occludes the active site.

    Evidence TIPRL crystal structure at 2.15 Å, mutagenesis, pull-down, HDX-MS and docking

    PMID:27489114

    Open questions at the time
    • Cellular consequence of TIPRL-mediated active-site blockade not quantified here
    • No structure of full PP2Ac-TIPRL complex
  10. 2018 High

    Established PPP2CA as an intellectual-disability gene and dissected how de novo variants impair activity, subunit binding and methylation by haploinsufficient or dominant-negative mechanisms.

    Evidence Functional expression, phosphatase activity, A/B-subunit Co-IP and methylation assays across patient variants

    PMID:30595372

    Open questions at the time
    • In vivo neurodevelopmental mechanism not modeled
    • Substrate-level consequences in neurons not defined
  11. 2018 High

    Linked glucose-sensing through Cav1.3/CAMK1/PPME1 to PP2Ac demethylation and RIPK1-dependent cell death, defining a metabolic control of PP2Ac inactivation.

    Evidence Channel pharmacology, CAMK1/PPME1 knockdown and demethylation/cell-death assays

    PMID:29317521

    Open questions at the time
    • Direct RIPK1 dephosphorylation by PP2Ac not formally shown
    • B-subunit specifying RIPK1 targeting unknown
  12. 2020 High

    Showed CDK1 directly phosphorylates a PP2Ac threonine to disrupt PP2A-B55 and promote mitotic entry, adding a direct layer to CDK1-PP2A crosstalk.

    Evidence Quantitative chemical proteomics with holoenzyme enrichment and kinase profiling

    PMID:32900880

    Open questions at the time
    • Precise threonine residue and its structural effect not fully resolved
    • In vivo cell-cycle requirement not tested
  13. 2020 High

    Demonstrated that widely used phospho-Tyr307 antibodies are non-specific and instead report Leu309 methylation and Thr304 phosphorylation, forcing reinterpretation of prior PP2Ac regulatory studies.

    Evidence Targeted mass spectrometry and antibody testing with phosphomimetic mutants, replicated by two groups

    PMID:32130915 PMID:32130916

    Open questions at the time
    • Physiological role of genuine pTyr307 remains undefined
    • Does not establish the true functional reader of these modifications
  14. 2021 High

    Connected PP2Ac to Hippo/YAP signaling and metabolism by showing PDCD10-stimulated PP2Ac dephosphorylates YAP to drive tumor migration, and methylation-dependent PP2Ac regulates macrophage mitophagy.

    Evidence Co-IP, phosphatase activity, siRNA epistasis and LB100 with xenografts; methylation manipulation with mitophagy readouts

    PMID:33912173 PMID:34521817

    Open questions at the time
    • Direct YAP dephosphorylation site not mapped
    • B-subunit directing YAP/MST targeting unspecified
  15. 2023 High

    Defined PP2Ac as a brake on innate antitumor immunity, restraining cGAS-STING type-I IFN signaling in glioma and, via the STRN4 holoenzyme, dephosphorylating MST1/2 to antagonize STING in macrophages.

    Evidence Genetic ablation/conditional KO, cGAS-STING and dephosphorylation assays, co-culture and in vivo tumor models

    PMID:36757811 PMID:37219874

    Open questions at the time
    • Direct STING-pathway substrate(s) in glioma not pinpointed
    • Generality across tumor types not established
  16. 2023 High

    Identified PTEN as a direct PP2Ac activator that dephosphorylates its C-terminus, and DCK Ser74 as a substrate controlling gemcitabine efficacy, linking PP2Ac to chemotherapy response.

    Evidence Direct binding, phosphatase and DCK phosphorylation assays with CDX/PDX models

    PMID:37437018

    Open questions at the time
    • Mechanism by which C-terminal dephosphorylation raises activity not structurally defined
    • Phosphatase activity of PTEN on PP2Ac vs scaffolding role
  17. 2024 High

    Provided an unbiased, system-wide definition of the PP2Ac substrate landscape and its pSP/pTP target motif, anchoring its broad regulatory reach.

    Evidence dTAG-mediated PPP2CA degradation with global phospho-proteomics

    PMID:38450154

    Open questions at the time
    • Holoenzyme/B-subunit assignment per substrate not resolved
    • Direct vs indirect substrates not fully distinguished
  18. 2024 High

    Identified PKCα/β phosphorylation of PP2Ac at Ser24 as the trigger of an IGBP1/alpha4-dependent PP2A switch that inactivates PI3K/AKT and drives JNK-dependent apoptosis.

    Evidence Phospho-MS, S24A/S24E mutants, specific antibody, Co-IP, PLA and TUNEL

    PMID:38419089

    Open questions at the time
    • Structural basis of the alpha4-mediated switch not resolved
    • Generality beyond GqPCR stimulation untested
  19. 2025 Medium

    Expanded the PP2Ac degradation network and modification control, identifying MKRN2 (K48/K41) and RCN2-UBR5 as degradation routes and Sirt2-controlled Lys136 acetylation as an activity switch.

    Evidence Co-IP, ubiquitination linkage/site mapping, acetylation and activity assays with KO mice and xenografts

    PMID:40523615 PMID:40959281 PMID:41411970

    Open questions at the time
    • Each E3-PP2Ac axis from single labs without cross-validation
    • Relative contribution of competing E3 ligases in vivo unclear
  20. 2025 Medium

    Established that PP2Ac carboxymethylation is tightly coupled to SAM/methionine availability and that demethylated PP2Ac suppresses cancer proliferation, linking one-carbon metabolism to PP2A activity.

    Evidence PME-1 overexpression, Leu309-deletion mimetic, SAM measurement and proliferation assays

    PMID:41008516

    Open questions at the time
    • Downstream substrate program of demethylated PP2Ac not defined
    • Single-lab gain-of-function evidence
  21. 2026 High

    Defined a PP2Ac-Rho1/RhoA-JNK migration axis and a Spry2-mediated sequestration mechanism controlling p65 dephosphorylation in NF-κB signaling.

    Evidence Drosophila genetic epistasis with AP-MS plus mammalian validation; Spry2-KO macrophages with Co-IP and inhibitor rescue

    PMID:41847846 PMID:42144974

    Open questions at the time
    • Direct Rho1/RhoA substrate relationship vs level control not fully resolved
    • Spry2 mechanism single-lab
  22. 2026 Medium

    Proposed reciprocal regulation between LRRK2 and PP2Ac in a neuronal context, with LRRK2 phosphorylating PP2Ac at Thr304 and PP2Ac dephosphorylating LRRK2.

    Evidence In vitro kinase/phosphatase and methylation assays with neuronal cell-death rescue (preprint)

    PMID:bio_10.1101_2025.10.07.680857

    Open questions at the time
    • Preprint, not peer-reviewed
    • Thr304-methylation crosstalk not validated in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How specific holoenzyme B-subunit compositions are matched to the >2,000 substrate landscape, and how the layered modification code (methylation, Ser24/Thr304/Thr phosphorylation, Lys136 acetylation) is integrated to dictate substrate choice, remains unresolved.
  • No comprehensive map linking individual B-subunits to defined substrates
  • Combinatorial effect of co-occurring PP2Ac modifications not deconvolved
  • Structures of substrate-engaged human holoenzymes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
IGBP1MID1MKRN2PDCD10PPP2R1BPTENTIPRLUBR5
Complex memberships
PP2A holoenzymePP2A-B55PP2A-B56PP2A/STRN4

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human PP2Ac functionally replaced endogenous PP2Ac in S. cerevisiae and bound the yeast PR65/A subunit (Tpd3p) forming a dimer. The invariant C-terminal leucine residue (Leu-309) is dispensable for basic function but truncated or active-site mutant forms of PP2Ac exert dominant-negative effects by titrating regulatory subunits/substrates into non-productive complexes; the L199P active-site mutant was catalytically impaired despite binding Tpd3p. Yeast complementation assay, mutagenesis, in vitro phosphatase activity assay, computer modeling of active site The Journal of biological chemistry High 10446173
2000 The C-terminal Leu-377 residue of yeast Pph22p (equivalent to human PP2Ac Leu-309) is required for binding of the PR55/B subunit (Cdc55p) but not the PR61/B' subunit (Rts1p). Mutation of this leucine enhanced sensitivity to microtubule destabilization, phenocopying cdc55Δ cells with impaired spindle checkpoint function, linking PP2Ac C-terminal leucine to mitotic checkpoint regulation via B-subunit binding. Yeast genetics, in vitro phosphatase activity assay, yeast two-hybrid/binding assay, phenotypic analysis with microtubule-destabilizing drugs Molecular & general genetics : MGG High 11129046
2003 Purified PP2Ac (but not PP4c or PP6c) bound to GST-alpha4 in pull-down assays and co-immunoprecipitated with endogenous and ectopic myc-tagged alpha4. The alpha4/PP2Ac interaction was disrupted by okadaic acid and microcystin-LR (phosphatase inhibitors) but was unaffected by rapamycin, implying the alpha4 binding site on PP2Ac includes the phosphatase catalytic domain. GST pull-down, co-immunoprecipitation, microcystin-Sepharose affinity purification, pharmacological inhibition Protein expression and purification Medium 12963337
2004 Missense mutations and deletions within the PP2A-Aβ subunit (PPP2R1B) at amino acids 412–601 (the PP2Ac-binding region) inhibited co-immunoprecipitation of PP2A-Aβ and PP2Ac, demonstrating that this region of the A subunit is required for physical interaction with the catalytic subunit. Co-immunoprecipitation from colorectal cancer tissues, sequence analysis Oncology reports Medium 14767517
2005 Alpha4 interacts with S6K1 through PP2Ac; pull-down assays defined that S6K1 binds the region from aa 88–309 of PP2Ac, while alpha4 binds two separated regions (aa 19–22 and aa 150–164) of PP2Ac. Stimulation of B cells with LPS induced the interaction of alpha4/PP2Ac with S6K1, suggesting alpha4 regulates S6K1 activity through PP2Ac. Co-immunoprecipitation, pull-down assay with deletion constructs, LPS stimulation of primary B cells Biochemical and biophysical research communications Medium 15796902
2006 CaMKIIα associates with PP2Ac and alpha4 in brain neurons. Neuron-specific alpha4 knockout mice showed increased CaMKIIα activity in hippocampus and impaired learning/memory. Alpha4 and PP2Ac were localized in the cytoplasm (not in the PSD), indicating cytoplasmic dephosphorylation of CaMKIIα by the alpha4/PP2Ac complex. Co-immunoprecipitation, neuron-specific conditional knockout mouse, behavioral assays (water maze, shuttle-box), subcellular fractionation/localization Brain research High 16516168
2007 siRNA-mediated depletion of PP2Ac in pancreatic INS-1 832/13 β-cells markedly attenuated PP2A activity and glucose-stimulated insulin secretion (GSIS). PP2Ac was detected in all subcellular fractions (cytosol > microsomes > secretory granules = nucleus > mitochondria), and its catalytic activity (regulated by carboxylmethylation) is required for GSIS signaling. siRNA knockdown, phosphatase activity assay, GSIS measurement, subcellular fractionation Endocrine Medium 17906371
2013 PP2Ac suppression (chemical or siRNA) in T-cells resulted in sustained phosphorylation of MEK and ERK after stimulation, increased DNMT enzyme activity, and DNA hypermethylation. Conversely, elevated PP2Ac dephosphorylates MEK/ERK to reduce DNMT1 expression and promote DNA hypomethylation, placing PP2Ac upstream of the MEK/ERK/DNMT1 axis in T-cell epigenetic regulation. siRNA knockdown, pharmacological inhibition, MEK/ERK phosphorylation assays, DNMT enzyme activity assay, gene expression analysis The Journal of biological chemistry High 23775084
2013 MID1 E3 ubiquitin ligase catalyzes in vitro ubiquitination of PP2Ac in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced. Bbox1 domain mutations found in X-linked Opitz syndrome abolish alpha4 polyubiquitination but not PP2Ac ubiquitination, indicating distinct MID1 substrate-binding mechanisms for PP2Ac versus alpha4. In vitro ubiquitination assay, domain deletion/mutation constructs PloS one High 25207814
2013 EDD E3 ubiquitin ligase binds the C-terminus of alpha4 and promotes polyubiquitination and proteasomal degradation of PP2Ac; siEDD knockdown reduced polyubiquitinated PP2Ac species, and progesterone induction of EDD correlated with decreased PP2Ac levels. Co-immunoprecipitation with alpha4 deletion constructs, siRNA knockdown, proteasomal inhibitor (MG132) treatment, Western blot Molecular and cellular endocrinology Medium 24145130
2014 PPP2CA restoration in prostate cancer cells decreased nuclear accumulation and transcriptional activity of β-catenin and NF-κB. Akt mediated PPP2CA loss-induced nuclear accumulation of β-catenin/NF-κB through inactivation of Gsk3-β and IκB-α, respectively. Restitution of β-catenin/NF-κB activity abrogated PPP2CA-induced reversal of EMT. Stable overexpression/silencing, luciferase promoter-reporter assay, immunoblot, immunofluorescence, orthotopic mouse model British journal of cancer High 24642616
2014 Gi-coupled receptor stimulation (A1R, M2, AT2) induces PP2Ac carboxylmethylation at Leu309 in adult rat ventricular myocytes via a Gβγ-PI3K signaling pathway. A1R stimulation increased PP2Ac association with its methyltransferase LCMT-1 and promoted PP2Ac translocation to the particulate fraction; these effects were blocked by PI3K inhibition or Gαt1 expression. Carboxylmethylation assay, pharmacological receptor stimulation, adenoviral Gαt1 expression, subcellular fractionation, co-immunoprecipitation PloS one High 24475092
2016 TIPRL crystal structure solved at 2.15 Å reveals a conserved cleft that binds the C-terminal tail of PP2Ac. Mutagenesis, pull-down, and hydrogen/deuterium exchange mass spectrometry confirmed TIPRL preferentially binds the unmodified (unmethylated) PP2Ac C-terminal peptide (DYFL) over the tyrosine-phosphorylated version. A docking model suggests TIPRL blocks the phosphatase active site. Crystal structure determination, mutagenesis, GST pull-down, hydrogen/deuterium exchange mass spectrometry, docking modeling Scientific reports High 27489114
2016 PP2Ac (alpha4/PP2Ac complex) dephosphorylates CaMKIIα in the cytoplasm, regulating its activity and influencing learning/memory. PP2Ac and alpha4 are localized in the cytoplasm and not in the post-synaptic density, indicating compartment-specific regulation of CaMKIIα. Conditional neuronal knockout, co-immunoprecipitation, subcellular fractionation, overexpression in neuronal cell lines Brain research High 16516168
2016 PP2Ac promotes Raf-MEK-ERK signaling in endothelial cells; inhibition of PP2Ac by okadaic acid or siRNA depletion led to significant inactivation of Raf-MEK-ERK and reduced glutaminolysis (measured by cellular glutamate levels and KGA expression). TGF-β1-induced glutaminolysis required PP2Ac-dependent Raf-MEK-ERK activation. Pharmacological inhibition (okadaic acid), siRNA knockdown, MEK inhibitor (U0126), Western blot, glutamate measurement PloS one Medium 27612201
2017 DDX3 forms a complex with PP2A-C and IKK-β (identified by co-immunoprecipitation and mass spectrometry). DDX3 modulates PP2A-C activity by controlling phosphorylation of PP2A-C, enabling PP2A-C to dephosphorylate IKK-β and regulate NF-κB signaling; this regulatory effect was independent of DDX3's ATPase or helicase activity. Co-immunoprecipitation, mass spectrometry, phosphorylation assays, siRNA knockdown Oncotarget Medium 28402257
2018 PP2Ac promotes DNA hypomethylation by dephosphorylating MEK/ERK, reducing DNMT1 expression. De novo PPP2CA mutations in patients with intellectual disability showed mutation-specific biochemical distortions including poor expression, altered A-subunit and B-subunit binding, impaired phosphatase activity, and impaired C-terminal methylation. Four variants caused complete PP2A dysfunction consistent with haploinsufficiency; four others had dominant-negative mechanisms correlating with severe ID. All pathogenic variants impair PP2A-B56δ functionality. Functional expression assays, phosphatase activity measurement, co-immunoprecipitation (A-subunit and B-subunit binding), methylation assays American journal of human genetics High 30595372
2018 Glucose deprivation triggers rapid plasma membrane depolarization and Ca2+ influx through Cav1.3, activating CAMK1, which together with PPME1 demethylates and inactivates PP2Ac. PP2Ac demethylation leads to RIPK1 phosphorylation and cell death. Glucose (but not its metabolizable function, since 2-DG also prevented it) prevents PP2Ac demethylation and cell death, identifying glucose as a signaling molecule protecting cells from depolarization-induced PP2Ac inactivation. Calcium channel pharmacology, CAMK1/PPME1 knockdown, PP2Ac demethylation assay, cell death assays (RIPK1 phosphorylation) Science signaling High 29317521
2019 LB-100, an experimental antitumor drug, is a catalytic inhibitor of both PP2Ac (PPP2CA) and PPP5C in vitro using purified enzymes. The crystal structure of PPP5C co-crystallized with LB-100 at 1.65 Å resolution revealed that the 7-oxabicyclo[2.2.1]heptane-2,3-dicarbonyl moiety coordinates with metal ions and conserved active-site residues shared by both PP2Ac and PPP5C. In vitro inhibition assay with purified enzymes, crystal structure determination (1.65 Å), cell-based genetic disruption of PPP5C Molecular cancer therapeutics High 30679389
2020 CDK1 directly phosphorylates a threonine residue on the PP2A catalytic subunit (PP2Ac), disrupting its holoenzyme formation with the regulatory subunit B55. This consequent decrease in PP2A-B55 substrate dephosphorylation promotes mitotic entry, constituting an additional layer of CDK1-PP2A regulation beyond the previously known indirect mechanism. Mass spectrometry-based chemical proteomics (PPP holoenzyme enrichment and quantification), kinase profiling, phosphorylation site identification Science signaling High 32900880
2020 PP2Ac phospho-Tyr307 antibodies (clones E155 and F-8) are not specific for phosphorylated Tyr307 but are instead sensitive to other PP2Ac modifications including Leu309 methylation and Thr304 phosphorylation. pTyr307 was identified by targeted mass spectrometry only under overexpression conditions, and none of the tested antibodies showed exclusive pTyr307 specificity, requiring reinterpretation of over 180 prior studies. Targeted mass spectrometry, antibody specificity testing with phosphomimetic mutants, Western blot Cell reports High 32130915 32130916
2020 Reduction in PP2Ac methylation (caused by ethanol-induced decrease in hepatic methylation capacity) led to increased degradation of the regulatory Bα subunit, promoting phosphorylation and nuclear exclusion of FOXO1, reducing FOXO1 transcriptional activity, and ultimately increasing TXNIP expression and hepatic lipid accumulation. Betaine supplementation (methyl donor), Western blot, phosphorylation analysis, subcellular fractionation, in vivo mouse model Toxicology letters Medium 32492475
2021 PDCD10 directly binds to PP2Ac and increases its enzymatic activity, leading to YAP dephosphorylation, YAP nuclear translocation and transcriptional activation. Knockdown of PP2Ac abolished PDCD10-mediated HCC cell migration, invasion and EMT; PP2Ac inhibitor LB100 restricted tumor growth and metastasis in HCC with high PDCD10 expression. Co-immunoprecipitation, phosphatase activity assay, siRNA knockdown, LB100 pharmacological inhibition, in vivo xenograft Cell death & disease High 34521817
2021 Taurine supplementation reduces SAM availability, which is sensed by LCMT-1 and PME-1 to reduce PP2Ac methylation. PP2Ac methylation was found necessary for M1 macrophage polarization including positive regulation of VDAC1 and PINK1, and its activation promotes PINK1-mediated mitophagy for metabolic adaptation to glycolysis during M1 polarization. Metabolic assays, Western blot for PP2Ac methylation, PINK1/VDAC1 expression, mitophagy flux assays, pharmacological inhibition of PP2Ac methylation (ABL127) Frontiers in immunology Medium 33912173
2021 TRPC1-mediated Ca2+ signaling increases levels of alpha4 and PP2Ac proteins and promotes alpha4/PP2Ac association in intestinal epithelial cells, enhancing cell migration after wounding. siRNA silencing of either alpha4 or PP2Ac destabilized alpha4/PP2Ac complexes and repressed migration; cellular polyamines regulated this pathway by controlling alpha4/PP2Ac expression and association. Stable TRPC1 overexpression, siRNA knockdown, co-immunoprecipitation, wound migration assay, polyamine manipulation Physiological reports Medium 33991460
2022 De novo PPP2CA missense variant p.Cys196Arg causes severe catalytic impairment, mildly reduced A-subunit binding, and moderately decreased binding to B/B55, B"/PR72, and most B56 subunits (except B56γ1), consistent with partial loss of function. C-terminal methylation and STRN3 binding were unaffected. In vitro phosphatase activity assay, co-immunoprecipitation for A and B subunit binding, methylation assay Frontiers in cell and developmental biology High 36531959
2023 PP2Ac deficiency in glioma cells enhanced dsDNA production and activated cGAS-STING-type I IFN signaling, increased MHC-I expression, and elevated tumor mutational burden. PP2Ac genetic ablation sensitized glioma tumors to immune-checkpoint blockade and radiotherapy, establishing PP2Ac as an inhibitor of cGAS-STING signaling in glioma cells. Genetic ablation (knockout), cGAS-STING signaling assays, MHC-I expression, dsDNA measurement, co-culture with DCs and T cells, in vivo tumor model with checkpoint blockade/radiotherapy, single-cell analysis Cancer research High 37219874
2023 PP2A with its specific B regulatory subunit STRN4 (forming PP2A/STRN4 holoenzyme) negatively regulates STING-type I IFN signaling in macrophages by dephosphorylating Hippo kinase MST1/2 and stabilizing YAP/TAZ to antagonize STING activation. STING agonists induced dissociation of PP2A from MST1/2 in normal but not in tumor-conditioned macrophages. Macrophage-specific PP2A conditional knockout, Co-IP (PP2Ac-STRN4-MST1/2 complex), dephosphorylation assay, STING signaling assay, in vivo tumor model The Journal of clinical investigation High 36757811
2023 PTEN directly binds to and dephosphorylates the C terminus of PP2Ac to increase its enzymatic activity; elevated PP2Ac activity in turn dephosphorylates deoxycytidine kinase (DCK) at Ser74 to diminish gemcitabine efficacy. PTEN deficiency therefore results in decreased PP2Ac activity and higher DCK phosphorylation, facilitating gemcitabine action. Direct binding assay, phosphatase activity assay, DCK phosphorylation assay, cell-based drug sensitivity assays, CDX and PDX xenograft models Science translational medicine High 37437018
2023 Luteolin directly binds to KDM4C, blocking KDM4C-induced histone demethylation of the PPP2CA promoter, inhibiting PPP2CA transcription. Reduced PPP2CA expression then impairs PPP2CA-mediated YAP dephosphorylation, thereby attenuating YAP activity and ovarian cancer stem cell stemness. Direct binding assay (luteolin-KDM4C), ChIP/promoter methylation, luciferase reporter, YAP phosphorylation assay, functional stemness assays Biomedicine & pharmacotherapy Medium 36804120
2024 dTAG-mediated selective degradation of PPP2CA in HEK293 cells followed by global phospho-proteomics identified 2,204 proteins with significantly increased phosphorylation, constituting a broad substrate landscape. A pSP/pTP motif was identified as the predominant PPP2CA target sequence. PPP2CA substrates are enriched for functions in spliceosome, cell cycle, RNA transport, and ubiquitin-mediated proteolysis. dTAG proteolysis-targeting chimera degradation of knock-in dTAG-PPP2CA, unbiased global phospho-proteomics, immunoblotting validation iScience High 38450154
2024 PKC (classical isoforms PKCα and PKCβ, but not novel PKCδ or PKCε) phosphorylates PP2Ac at Ser24. This phosphorylation is necessary and sufficient to trigger the PP2A switch (involving IGBP1/alpha4), inducing dephosphorylation and inactivation of PI3K and AKT, and leading to JNK-dependent apoptosis upon GqPCR activation. Phospho-mass spectrometry to identify Ser24 site, specific phospho-antibody generation, S24A and S24E substitution mutants, co-immunoprecipitation, proximity ligation assay, TUNEL apoptosis assay Cell communication and signaling : CCS High 38419089
2024 PP2Ac regulates ULK1 phosphorylation (dephosphorylation at Ser637) during osteoclastogenesis to control autophagy. mTORC1 inhibition facilitated PP2Ac expression, and PP2Ac-mediated autophagy was dependent on ULK1 phosphorylation activity. Knockdown or inhibition of PP2Ac weakened autophagy during osteoclastogenesis. siRNA knockdown, phosphorylation assay (ULK1 Ser637), mTORC1 inhibition, in vivo OA rat model Advanced science Medium 39041921
2025 MKRN2 E3 ligase interacts with PPP2CA and promotes K48-linked ubiquitination at PPP2CA's K41 residue, leading to proteasomal degradation of PPP2CA. Consequently, MKRN2-mediated PPP2CA repression increased β-catenin phosphorylation and decreased its levels, inactivating Wnt signaling in clear cell renal cell carcinoma. Co-immunoprecipitation, ubiquitination assay (K48-linkage, K41 site identification), Western blot, in vivo xenograft International journal of biological sciences Medium 40959281
2025 Sirt2 regulates PP2Ac activation through controlling PP2Ac acetylation at Lys136. Colchicine enhances Sirt2 expression, which deacetylates and activates PP2Ac, leading to increased phosphorylation of NLRP3 at Ser5 and reduced NLRP3 inflammasome activation, thereby inhibiting vascular calcification. Phosphorylation/acetylation assays, Sirt2 knockout mice, PP2Ac activity assay, vascular calcification models in vitro and in vivo The Journal of biological chemistry Medium 40523615
2025 Carboxy-methylation of PP2Ac is highly sensitive to intracellular SAM levels. Overexpression of PME-1 (which demethylates PP2A) or expression of a Leu309-deleted unmethylated PP2A mimetic was sufficient to reduce cancer cell proliferation even in methionine-independent cells, establishing a mechanistic link between methionine/SAM availability, PP2Ac methylation status, and cell proliferation. PME-1 overexpression, Leu309-deleted PP2Ac expression, SAM measurement, cell proliferation assays Biomolecules Medium 41008516
2025 RCN2 facilitates PPP2CA ubiquitination and proteasomal degradation in a manner dependent on the HECT domain of UBR5 E3 ligase; RCN2 physically interacts with both PPP2CA and UBR5. This PPP2CA degradation activates PI3K-AKT signaling to promote ESCC metastasis and cisplatin resistance. Co-immunoprecipitation, GST pull-down, Western blot for ubiquitination, RNA-seq, LC-MS/MS, in vivo xenograft Drug resistance updates Medium 41411970
2025 LRRK2 phosphorylates PP2Ac at residue T304 in vitro; this LRRK2-mediated T304 phosphorylation alters C-terminal methylation of PP2Ac, impairing PP2A holoenzyme formation and catalytic activity. Reciprocally, PP2A dephosphorylates sites in the RocCOR-GTPase domain of LRRK2, de-stabilizing LRRK2 dimers and reducing its kinase activity. WT PPP2CA expression protected from LRRK2-G2019S-induced neuronal cell death, while T304 mutants failed to do so. In vitro dephosphorylation assay (PP2A on LRRK2), kinase assay (LRRK2 on PP2Ac T304), PP2Ac methylation assay, holoenzyme formation assay, neuronal cell death rescue experiment with WT vs. T304 mutant PP2CA bioRxivpreprint Medium bio_10.1101_2025.10.07.680857
2026 PP2Ac (Mts in Drosophila) is sufficient to trigger cell migration by activating the JNK signaling pathway. Genetic epistasis analyses in Drosophila showed Mts acts upstream of Slpr (MLK kinase) in the JNK cascade. Affinity purification-mass spectrometry identified Rho1 as a mediator; Mts activates JNK by increasing Rho1 protein levels, and Rho1 acts downstream of Mts/upstream of Slpr-JNK. PP2Ac also promoted cell migration in human pancreatic cancer cells associated with RhoA levels and JNK activation. Drosophila genetic epistasis (double mutant analysis), affinity purification-mass spectrometry (AP-MS), PP2AC overexpression in human PAAD cells, Western blot for RhoA/JNK FASEB journal High 42144974
2026 Spry2 sequesters PP2Ac upon LPS stimulation (Spry2 becomes serine-phosphorylated and associates with PP2Ac), preventing PP2Ac from dephosphorylating p65, thus heightening NF-κB nuclear translocation and cytokine production. In Spry2-deficient macrophages, PP2Ac freely interacts with p65, enhancing its dephosphorylation and reducing its nuclear translocation; PP2Ac inhibitor treatment rescued this defect. Co-immunoprecipitation, Spry2 knockout macrophages, PP2Ac inhibitor rescue, p65 nuclear translocation assay, cytokine measurement Journal of immunology Medium 41847846

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 86 23775084
2014 Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients. Lupus 65 25253569
2021 Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation. Frontiers in immunology 62 33912173
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 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
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 50 30679389
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
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
2023 PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma. Cancer research 41 37219874
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/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages. The Journal of clinical investigation 36 36757811
2011 Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. Arthritis and rheumatism 36 21590681
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
2023 Luteolin directly binds to KDM4C and attenuates ovarian cancer stemness via epigenetic suppression of PPP2CA/YAP axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 36804120
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 25 33609307
2021 Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation. Cell death & disease 25 34521817
2018 Ca2+-dependent demethylation of phosphatase PP2Ac promotes glucose deprivation-induced cell death independently of inhibiting glycolysis. Science signaling 25 29317521
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 YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification. Biological procedures online 23 36870954
2023 ALA reverses ABA-induced stomatal closure by modulating PP2AC and SnRK2.6 activity in apple leaves. Horticulture research 22 37287446
2016 Glutaminolysis Was Induced by TGF-β1 through PP2Ac Regulated Raf-MEK-ERK Signaling in Endothelial Cells. PloS one 22 27612201
2023 PTEN deficiency facilitates gemcitabine efficacy in cancer by modulating the phosphorylation of PP2Ac and DCK. Science translational medicine 20 37437018
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
2020 Challenges and Reinterpretation of Antibody-Based Research on Phosphorylation of Tyr307 on PP2Ac. Cell reports 18 32130915
2024 Mapping the substrate landscape of protein phosphatase 2A catalytic subunit PPP2CA. iScience 16 38450154
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 Drug-resistant exosome miR-99b-3p induces macrophage polarization and confers chemoresistance on sensitive cells by targeting PPP2CA. International immunopharmacology 14 39298813
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 14 37579989
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
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 13 34363881
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
2022 KHSRP modulated cell proliferation and cell cycle via regulating PPP2CA and p27 expression in Wilms tumor. Cellular signalling 12 36029941
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
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 10 28904398
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 9 38419089
2024 PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39041921
2022 PPP2CA Is a Novel Therapeutic Target in Neuroblastoma Cells That Can Be Activated by the SET Inhibitor OP449. Frontiers in oncology 9 35814385
2024 PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer. Digestive diseases and sciences 8 38637456
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
2023 Volatile oil of Angelica sinensis Radix improves cognitive function by inhibiting miR-301a-3p targeting Ppp2ca in cerebral ischemia mice. Journal of ethnopharmacology 7 38154524
2021 PP2A-C may be a promising candidate for postmortem interval estimation. International journal of legal medicine 7 33409557
2024 Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA. International journal of nanomedicine 6 39253060
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
2025 Colchicine inhibits vascular calcification by suppressing inflammasome activation through the enhancement of the Sirt2-PP2Ac signaling pathway. The Journal of biological chemistry 5 40523615
2024 TaNAC1 boosts powdery mildew resistance by phosphorylation-dependent regulation of TaSec1a and TaCAMTA4 via PP2Ac/CDPK20. The New phytologist 5 39183373
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 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
2025 Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction. Communications biology 4 39838082
2025 Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation. Biomolecules 4 41008516
2024 gp78-regulated KAP1 phosphorylation induces radioresistance in breast cancer by facilitating PPP1CC/PPP2CA ubiquitination. iScience 4 39297166
2023 ALA induces stomatal opening through regulation among PTPA, PP2AC, and SnRK2.6. Frontiers in plant science 4 37711306
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 4 38069840
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 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
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 3 37377738
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 Triptolide targets PPP2CA/ITGA5 axis to suppress lactate-driven ovarian cancer progression. Chinese medicine 2 40770810
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
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 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 1 41411970
2023 PP2Ac knockdown attenuates lipotoxicity‑induced pancreatic β‑cell dysfunction and apoptosis. Experimental and therapeutic medicine 1 37928506
2026 Isorhyncophylline Targets PP2AC to Modulate YAP to Inhibit Endothelial Cell Inflammation. Phytotherapy research : PTR 0 41626858
2026 Phenotypic Analysis of Mice with Conditional Knockout of PPP2CA in Colonic Tissues. Digestive diseases and sciences 0 41774332
2026 O-GlcNAcylation of IGF2BP2 promotes angiogenesis after ischemic stroke by stabilizing PPP2CA in an m6A-dependent manner : O-GlcNAcylation of IGF2BP2 alleviates ischemic brain injury. Journal of translational medicine 0 41832533
2026 Sprouty2 modulates NF-κB signaling by sequestering the phosphatase PP2Ac in LPS-stimulated macrophages. Journal of immunology (Baltimore, Md. : 1950) 0 41847846
2026 Identification of peptides interfering with the PP2Ac And LRRK2 interaction. Biochimica et biophysica acta. Proteins and proteomics 0 41990985
2026 Mts/PP2AC Induces Cell Migration via Rho1-Slpr-Mediated JNK Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 42144974
2025 Mutations Upstream of ppp2ca Affect Body Weight in Asian Seabass. Marine biotechnology (New York, N.Y.) 0 41114894
2023 Establishment of a PPP2CA homozygous knockout human embryonic stem cell line via CRISPR/Cas9 system. Stem cell research 0 36724553
2018 Purification of Target Proteins from Native Tissues: CCT Complex from Bovine Testes and PP2Ac from Porcine Brains. Methods in molecular biology (Clifton, N.J.) 0 29247302
2018 [Inhibition of demethylation of protein phosphatase 2A catalytic subunit (PP2Ac) promotes M1 polarization of macrophages]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 30381122

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