Affinage

PPP2R5C

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform · UniProt Q13362

Length
524 aa
Mass
61.1 kDa
Annotated
2026-06-10
45 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP2R5C (B56γ) is a substrate-targeting regulatory subunit of the PP2A heterotrimeric phosphatase that operates as a context-dependent tumor suppressor by directing catalytic activity onto specific phosphoprotein substrates (PMID:17245430, PMID:15466190). Its central role is in the DNA-damage response: ATM-dependent phosphorylation of p53 at Ser15 recruits B56γ, which dephosphorylates p53 at Thr55 to stabilize the protein, drive p21 transcription, and impose G1 arrest, while ATM also phosphorylates B56γ itself at Ser510 to block MDM2-mediated ubiquitination and stabilize the subunit (PMID:17245430, PMID:17967874, PMID:21460856, PMID:29988038). B56γ engages the PP2A AC core through its first HEAT repeat and contacts substrates through a separate substrate-binding domain, so cancer-associated mutations fall into two mechanistic classes—loss of AC-core assembly (e.g. C39R) abolishing all activity, or loss of specific substrate contacts (e.g. F395C) selectively crippling p53-dependent suppression (PMID:20473327, PMID:22315229, PMID:23723076). Beyond p53, B56γ-PP2A dephosphorylates AKT (Thr308/Ser473), Drp1 at Ser616 to restrain mitophagy, Ebp1 at Ser335 to govern nucleolar ribosome biogenesis, and CREB/ATF1, and it negatively regulates NF-κB in T-cell receptor signaling by opposing IKK phosphorylation (PMID:24719332, PMID:20730097, PMID:35811356, PMID:35697120, PMID:42097318). The subunit is recruited to plasma-membrane platforms via an LxxIxE short linear motif in liprin-α1 to support cell spreading, invasion, and migration, localizes isoform-specifically to the Golgi to modulate vesicle transport, and maintains spindle-assembly-checkpoint integrity by stabilizing BubR1 (PMID:28562161, PMID:12547706, PMID:36171301). B56γ is required for cardiac development, acting in genetic concert with B56δ (PMID:24425002, PMID:35415460), and is exploited as the host receptor for HTLV-1 retroviral integrase through a conserved SLiM, as resolved by structural studies (PMID:33028863). De novo missense variants in PPP2R5C cause a neurodevelopmental disorder in the Houge-Janssens syndrome spectrum, with a likely dominant-negative effect on substrate dephosphorylation (PMID:39978342).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2007 High

    Established that B56γ is the PP2A subunit responsible for dephosphorylating p53 at Thr55 during the DNA-damage response, linking PP2A to p53 stabilization and apoptosis.

    Evidence RNAi knockdown, reciprocal Co-IP, and apoptosis/transformation readouts in damaged cells

    PMID:17245430

    Open questions at the time
    • Did not define how the B56γ-p53 interaction is regulated
    • No structural basis for substrate recognition
  2. 2007 High

    Showed that ATM-driven p53 Ser15 phosphorylation is the trigger that recruits B56γ, explaining how damage signaling is converted into targeted dephosphorylation and growth arrest.

    Evidence Co-IP with phospho-site mutant p53, cell-cycle and anchorage-independent growth assays, ATM inhibition

    PMID:17967874

    Open questions at the time
    • Did not address regulation of B56γ protein levels
    • p53-independent functions not separated
  3. 2011 High

    Resolved how B56γ itself is controlled, showing ATM phosphorylates B56γ at Ser510 to block MDM2-mediated degradation and upregulate the subunit upon damage.

    Evidence In vitro kinase assay, ubiquitination assay, Ser510 mutagenesis, transformation assays

    PMID:21460856

    Open questions at the time
    • MDM2 ubiquitination site on B56γ not mapped
    • In vivo relevance of Ser510 not tested in animals
  4. 2010 High

    Defined a discrete substrate-binding domain by showing a lung-cancer mutation F395C selectively abolishes p53 binding and p21 activation, separating p53-dependent from p53-independent tumor suppression.

    Evidence Cancer-variant mutagenesis, Co-IP, dephosphorylation and p21 luciferase reporter assays

    PMID:20473327

    Open questions at the time
    • Identity of p53-independent substrates not established
    • No structural model of the domain
  5. 2012 High

    Mapped HEAT repeat 1 as the AC-core docking site and showed mutation C39R there disrupts holoenzyme assembly, abolishing all suppressor activity.

    Evidence Co-IP, HEAT-repeat mutagenesis, dephosphorylation and transformation assays

    PMID:22315229

    Open questions at the time
    • No reconstitution of the assembled holoenzyme
    • Did not enumerate p53-independent substrates lost
  6. 2013 Medium

    Consolidated a two-class mutational model in which cancer-derived variants either lose AC-core binding (global loss) or lose specific substrate contacts (selective loss).

    Evidence Co-IP and functional assays across multiple cancer-derived mutants

    PMID:23723076

    Open questions at the time
    • No in vitro reconstitution
    • Unknown p53-independent substrates remain unidentified
  7. 2004 High

    Placed B56γ-PP2A as the key target of SV40 small-t transforming activity, by showing its knockdown substitutes for ST in fully transforming human cells.

    Evidence shRNA knockdown, full transformation assay, expression profiling

    PMID:15466190

    Open questions at the time
    • Substrates mediating transformation not pinpointed
    • Mechanism of ST inhibition of B56γ not detailed here
  8. 2010 Medium

    Extended substrate range beyond p53 by showing B56γ-PP2A opposes ATM/CK1-2 phosphorylation of CREB and ATF1.

    Evidence Phosphorylation assays with B56γ manipulation and CK1/2 inhibition

    PMID:20730097

    Open questions at the time
    • No in vitro reconstitution of direct dephosphorylation
    • Functional consequence on CREB/ATF1 targets unresolved
  9. 2014 Medium

    Identified B56γ as a brake on NF-κB in T-cell receptor signaling, opposing IKK/IκBα phosphorylation and limiting IL-2 and proliferation.

    Evidence siRNA screen with NF-κB reporter, phosphorylation Western blots, cytokine and proliferation assays

    PMID:24719332

    Open questions at the time
    • Direct substrate within the IKK module not reconstituted
    • Single cell-line context (Jurkat/T cells)
  10. 2007 Medium

    Discovered liprin-α1 as a B56γ binding partner distinct from its transforming PP2A complexes, implicating B56γ in cell morphology.

    Evidence Tandem affinity purification/MS, Co-IP, RNAi

    PMID:18235218

    Open questions at the time
    • Molecular basis of the interaction not defined at this stage
    • Functional pathway downstream of morphology change unknown
  11. 2022 High

    Defined the liprin-α1 interaction mechanistically as an LxxIxE SLiM that docks B56γ, recruiting the PP2A holoenzyme to plasma-membrane platforms to drive spreading, invasion, and motility.

    Evidence SLiM mutagenesis, reciprocal Co-IP, fractionation, live-cell imaging, invasion assay

    PMID:36171301

    Open questions at the time
    • Membrane-platform substrates dephosphorylated by B56γ not identified
    • Tested mainly in breast cancer cells
  12. 2003 Medium

    Identified isoform-specific Golgi localization of B56γ and linked B56γ-PP2A to suppression of ER-to-membrane vesicle transport and directional migration.

    Evidence Immunofluorescence, sucrose-gradient fractionation, vesicle transport and migration assays

    PMID:12547706

    Open questions at the time
    • No Golgi substrate identified
    • Truncated Δγ1 variant complicates interpretation
  13. 2017 Medium

    Showed B56γ is specifically required to stabilize BubR1 and maintain the spindle-assembly checkpoint, with its loss causing premature mitotic progression and missegregation.

    Evidence B56γ knockout primary cells, nocodazole arrest, BubR1 Western blot, segregation analysis

    PMID:28562161

    Open questions at the time
    • Direct dephosphorylation target stabilizing BubR1 not defined
    • Whether BubR1 is a direct B56γ substrate untested
  14. 2020 High

    Provided atomic structures showing HTLV-1 integrase hijacks B56γ as a host factor via a conserved SLiM, defining a viral interface on the PP2A subunit.

    Evidence X-ray crystallography and single-particle cryo-EM of the integrase–B56γ complex

    PMID:33028863

    Open questions at the time
    • Functional consequence of integrase binding for viral integration not detailed here
    • Whether binding redirects PP2A activity unknown
  15. 2018 Medium

    Connected upstream transcriptional control to function, showing AP-1/CREBH ER-stress signaling transactivates B56γ, which then dephosphorylates p-Thr55-p53 to enforce arrest and apoptosis in HBx-expressing hepatocytes.

    Evidence Luciferase reporter, Co-IP, knockdown/overexpression, cell-cycle/apoptosis assays

    PMID:29988038

    Open questions at the time
    • Direct AP-1 binding to promoter not structurally mapped here
    • Context limited to HBx hepatocytes
  16. 2022 Medium

    Expanded the suppressor substrate set in liver cancer, showing B56γ dephosphorylates AKT (Thr308/Ser473) to inhibit HBx-driven growth, migration, and invasion.

    Evidence Phospho-mimetic mutagenesis, Co-IP, xenograft, migration/invasion assays

    PMID:35811356

    Open questions at the time
    • Direct in vitro dephosphorylation of AKT not reconstituted
    • HBx-specific context
  17. 2022 Medium

    Linked B56γ to mitochondrial quality control by showing dephosphorylation of Drp1 Ser616 disrupts Drp1-Rab7 coupling, inhibiting mitophagy and enhancing apoptosis under chemotherapy.

    Evidence Co-IP of Drp1-Rab7, dephosphorylation Western blot, xenograft, apoptosis flow cytometry, contact-site imaging

    PMID:35697120

    Open questions at the time
    • Single tumor context (HCC)
    • Whether the holoenzyme acts directly at mitochondria unresolved
  18. 2002 Medium

    First in vivo evidence linking B56γ to development, showing lung overexpression disrupts distal differentiation with loss of beta-catenin, implicating Wnt modulation.

    Evidence Transgenic mouse, in situ hybridization, IHC, beta-catenin Western blot

    PMID:12003782

    Open questions at the time
    • Direct beta-catenin dephosphorylation not shown
    • Overexpression rather than physiological loss
  19. 2014 Medium

    Demonstrated a developmental requirement in heart and neuromuscular function via B56γ knockout causing ventricular septal defects and cardiomyocyte apoptosis.

    Evidence Knockout mouse, histology, IHC, TUNEL, behavioral testing

    PMID:24425002

    Open questions at the time
    • Cardiac substrates of B56γ not identified
    • Mechanism of apoptosis not defined
  20. 2021 Medium

    Revealed redundancy in development by showing combined B56γ/B56δ loss is embryonic-lethal with single-outflow-vessel hearts, while single knockouts survive.

    Evidence CRISPR/Cas9n double-knockout mice, embryo phenotyping, cardiac histology

    PMID:35415460

    Open questions at the time
    • Shared substrate underlying redundancy unknown
    • Outflow-tract mechanism not defined
  21. 2010 Medium

    Identified a transcriptional input by showing NRL directly binds the Ppp2r5c promoter to drive expression during photoreceptor development.

    Evidence EMSA, ChIP, luciferase reporter

    PMID:21078119

    Open questions at the time
    • Functional role of B56γ in photoreceptors not tested
    • Downstream substrates unknown
  22. 2025 Medium

    Established PPP2R5C as a disease gene, showing de novo missense variants cause a neurodevelopmental disorder through impaired substrate or C-subunit binding and a likely dominant-negative effect.

    Evidence Patient variant cohort, structural mapping, PP2A catalytic activity assays

    PMID:39978342

    Open questions at the time
    • Specific neuronal substrates driving phenotype not defined
    • Dominant-negative mechanism not directly reconstituted
  23. 2026 Medium

    Added a nucleolar/senescence axis, showing B56γ dephosphorylates Ebp1 Ser335 to suppress rRNA transcription and trigger p53/p21-dependent neuronal senescence under nanoplastic stress.

    Evidence In vitro dephosphorylation, mouse exposure model, nucleolar imaging, pre-rRNA assay, LB-100 rescue

    PMID:42097318

    Open questions at the time
    • Generalizability beyond nanoplastic stress unknown
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full catalogue of B56γ-specific substrates underlying its p53-independent suppressor, developmental, and neurodevelopmental functions remains incomplete, and no reconstituted structural model explains how the assembled holoenzyme selects most of its targets.
  • p53-independent substrates largely unidentified
  • No structure of B56γ holoenzyme bound to a physiological substrate
  • Disease dominant-negative mechanism not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005634 nucleus 1 GO:0005730 nucleolus 1 GO:0005794 Golgi apparatus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
AKTBUBR1DNM1L/DRP1MDM2PA2G4/EBP1PPP1R9A/LIPRIN-Α1PPP2CATP53
Complex memberships
PP2A holoenzyme (B56γ-A-C heterotrimer)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 B56γ1 and B56γ3 isoforms of PP2A mediate dephosphorylation of p53 at Thr55 in response to DNA damage. Ablation of B56γ by RNAi abolishes Thr55 dephosphorylation, reduces p53 stabilization, Bax expression, and cell apoptosis. Endogenous B56γ protein level and association with p53 increase after DNA damage. RNAi knockdown, co-immunoprecipitation, Western blot, cell proliferation and transformation assays The EMBO journal High 17245430
2007 ATM-dependent phosphorylation of p53 at Ser15 is required for the enhanced interaction between B56γ and p53 after DNA damage. This Ser15-phosphorylation-mediated p53-B56γ interaction is required for B56γ3-induced G1 cell cycle arrest and inhibition of anchorage-independent growth. Co-immunoprecipitation, mutant p53 constructs, cell cycle analysis, anchorage-independent growth assays, ATM inhibition Molecular and cellular biology High 17967874
2011 ATM directly phosphorylates B56γ3 at Ser510 after DNA damage, leading to increased B56γ3-PP2A complex formation and directed PP2A phosphatase activity toward p53, activating tumor-suppressive functions. Under normal growth conditions, B56γ3 is targeted for ubiquitination and degradation by MDM2, and ATM-mediated phosphorylation at Ser510 blocks MDM2-mediated B56γ3 ubiquitination, upregulating B56γ3 protein levels. In vitro kinase assay, Co-IP, ubiquitination assay, mutagenesis (Ser510 substitution), cell proliferation and transformation assays Oncogene High 21460856
2010 A B56γ mutation F395C identified in lung cancer disrupts the B56γ-p53 interaction, abolishes p53 Thr55 dephosphorylation, prevents transcriptional activation of p21, and eliminates the p53-dependent tumor-suppressive function of B56γ-PP2A. A domain of B56γ required for p53 interaction was identified, distinguishing p53-dependent from p53-independent tumor suppressive functions. Co-immunoprecipitation, site-directed mutagenesis, dephosphorylation assays, luciferase reporter (p21 transcription), cell transformation assays Oncogene High 20473327
2012 HEAT repeat 1 of B56γ is required for interaction with the PP2A AC core (scaffolding A and catalytic C subunits) and for B56γ-PP2A tumor-suppressive function. A tumor-associated mutation C39R within HEAT repeat 1 disrupts the AC core interaction, abolishing both p53-dependent and p53-independent tumor suppression. Co-immunoprecipitation, site-directed mutagenesis, dephosphorylation assays, cell proliferation and transformation assays The Journal of biological chemistry High 22315229
2013 B56γ tumor-associated mutations from human cancer samples lose tumor-suppressive activity by two distinct mechanisms: disruption of interaction with the PP2A AC core (abolishing all substrate dephosphorylation), or disruption of specific substrate interactions (p53 and unknown proteins), causing partial loss of either p53-dependent or p53-independent tumor suppression. Co-immunoprecipitation, mutagenesis of cancer-derived variants, p53 dephosphorylation assay, cell proliferation and transformation assays Molecular cancer research : MCR Medium 23723076
2004 Knockdown of PP2A B56γ subunit can substitute for SV40 small tumor antigen (ST) expression to fully transform human cells (expressing LT, hTERT, and Ras-V12), establishing B56γ-PP2A as the relevant target of ST's transforming activity. ST promotes cell transformation through integrin signaling, src phosphorylation, and NF-κB activation. shRNA knockdown, transformation assay, gene expression profiling, pharmacological inhibition Cancer research High 15466190
2014 B56γ is a negative regulator of NF-κB in TCR signaling in T cells. B56γ silencing induced increased IKK and IκBα phosphorylation upon TCR stimulation, enhanced NF-κB activity and target gene expression (including IL-2), and increased T cell proliferation. B56γ was identified by siRNA screen in Jurkat cells using an NF-κB-responsive reporter. siRNA screen, NF-κB luciferase reporter, Western blot (IKK and IκBα phosphorylation), cytokine quantification, cell proliferation assay The Journal of biological chemistry Medium 24719332
2010 PP2A with B56γ targeting subunit antagonizes ATM- and CK1/2-dependent phosphorylation of CREB and ATF1 in cells. B56γ-PP2A opposes phosphorylation at the conserved ATM/CK cluster on both transcription factors. Co-immunoprecipitation, phosphorylation assays, B56γ overexpression/knockdown, CK1/2 inhibition PloS one Medium 20730097
2002 Transgenic overexpression of B56γ in the lung (using SP-C promoter) disrupts distal lung differentiation and causes neonatal death, associated with loss of beta-catenin, suggesting B56γ modulates PP2A action on the Wnt/beta-catenin signaling pathway during lung airway morphogenesis. Transgenic mouse model, in situ hybridization, immunohistochemistry, beta-catenin Western blot American journal of physiology. Lung cellular and molecular physiology Medium 12003782
2014 PP2A-B56γ knockout mice develop incomplete ventricular septal defects and decreased ventricular cardiomyocytes, with cardiomyocyte apoptosis during mid-to-late gestation. B56γ is expressed in the nucleus of alpha-actinin-positive cardiomyocytes containing Z-bands during cardiac development. Mice also show decreased neuromuscular coordination and gripping strength, indicating a role in neuromuscular function. Transgenic knockout mouse, histology, immunohistochemistry, TUNEL apoptosis assay, behavioral testing Developmental dynamics Medium 24425002
2017 PP2A-B56γ is required for stability of BubR1 during nocodazole-induced spindle assembly checkpoint (SAC) arrest. In primary cells lacking B56γ, BubR1 is prematurely degraded and cells proceed through mitosis, resulting in abnormal chromosomal segregation. Inactivation of B56γ alone (without affecting other B56 family members) is sufficient to affect SAC efficiency. B56γ knockout primary cells, nocodazole arrest, Western blot (BubR1 levels), chromosome segregation analysis, fluorescence imaging of B56 subunit localization Cell cycle (Georgetown, Tex.) Medium 28562161
2003 B56γ1 and B56γ2 (but not B56γ3) localize to the Golgi complex (cis-Golgi) in melanoma cells, and the PP2A catalytic subunit co-fractionates with B56γ in the Golgi-enriched fraction. A truncated variant Δγ1 preferentially localizes to the trans-Golgi. Cells stably expressing Δγ1 show faster vesicle transport from ER to plasma membrane and elevated directional migration, suggesting B56γ-containing PP2A holoenzymes suppress vesicle transport. Immunofluorescence, subcellular fractionation/sucrose gradient, FLAG-tagged protein localization, vesicle transport assay, cell migration assay The American journal of pathology Medium 12547706
2007 Liprin-α1 interacts with PP2A B56γ as a novel binding partner identified by tandem affinity purification and mass spectrometry. B56γ-liprin-α1 complexes are distinct from PP2A complexes containing B56γ (i.e., liprin-α1 does not directly contribute to cell transformation). Suppression of liprin-α1 alters cell morphology. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, RNAi knockdown Cell cycle (Georgetown, Tex.) Medium 18235218
2022 Liprin-α1 contains an LxxIxE short linear motif (SLiM) in its N-terminal region that interacts specifically with B56γ regulatory subunits of PP2A. Two point mutations in the SLiM strongly reduce the interaction. B56γ mediates the interaction of liprin-α1 with the heterotrimeric PP2A holoenzyme. B56γ localizes to plasma membrane-associated platforms (PMAPs) in migrating breast cancer cells in a liprin-α1-dependent manner. Silencing B56γ inhibits cell spreading, invasion, motility, and lamellipodia dynamics to a similar extent as silencing liprin-α1. Co-immunoprecipitation, mutagenesis of SLiM motif, subcellular fractionation, live-cell imaging, RNAi knockdown, invasion assay Communications biology High 36171301
2020 The B56γ subunit of PP2A is the host factor bound by the HTLV-1 retroviral integrase (IN). Cryo-EM and X-ray crystallography structures reveal a tetrameric IN assembly bound to two molecules of B56γ via a conserved short linear motif on the integrase. X-ray crystallography, single-particle cryo-EM, structural determination of complex Nature communications High 33028863
2018 B56γ is transactivated by AP-1, which is regulated by ER stress-induced CREBH signaling in HBx-expressing hepatic cells. B56γ dephosphorylates p-Thr55-p53, triggering p53/p21 pathway-dependent G1 cell cycle arrest and apoptosis of HBx-expressing hepatocytes. Western blot, co-immunoprecipitation, gene knockdown/overexpression, cell cycle analysis, luciferase reporter assay Cell death & disease Medium 29988038
2022 B56γ inhibits HBV/HBx-dependent hepatocarcinogenesis by mediating dephosphorylation of AKT at Thr308 and Ser473. B56γ overexpression and site-directed mutagenesis mimicking dephosphorylation (AKTT308A, AKTS473A) inhibited cell growth, migration, and invasion in HBx-expressing HCC cells. Western blot, site-directed mutagenesis, co-immunoprecipitation, overexpression, xenograft mouse model, cell migration/invasion assays Cell proliferation Medium 35811356
2022 B56γ-mediated direct dephosphorylation of Drp1 at Ser616 inhibits the interaction between p-Drp1Ser616 and Rab7, thereby inhibiting mitophagy and increasing mitochondria-dependent apoptosis in HCC cells under chemotherapy treatment. Co-immunoprecipitation, Western blot (dephosphorylation), B56γ overexpression/knockdown, xenograft mouse model, flow cytometry (apoptosis), mitochondria-lysosome contact site imaging Biochemical pharmacology Medium 35697120
2003 A truncated isoform of B56γ (Δγ1) in metastatic melanoma BL6 cells impairs the cell-cycle checkpoint, leading to increased polyploidy and reduced apoptosis after irradiation, and promotes metastasis. Expression of Δγ1 in F10 cells reproduced the checkpoint aberration and enhanced metastatic ability. Gene transfection, irradiation, cell cycle analysis, apoptosis assay, in vivo tumor transplant and metastasis assay The American journal of pathology Medium 12507892
2004 A truncated B56γ variant (Δγ1) reduces irradiation-induced Mdm2 phosphorylation, which blocks irradiation-stimulated p53 accumulation and p53-target gene (Bax) induction, contributing to melanoma cell radioresistance. Stable transfection, Western blot (Mdm2 and p53 phosphorylation), RT-PCR (p53/Bax mRNA), apoptosis assay, in vivo irradiation Histology and histopathology Low 15024700
2021 Mice with both B56δ and B56γ inactivated (double knockout) arrest fetal development around E12 with hearts having a single outflow vessel, demonstrating strong genetic interaction between B56δ and B56γ that is necessary for heart development. Individual knockouts of B56δ or B56γ alone are not lethal. CRISPR/Cas9n knockout mouse generation, embryo phenotyping, cardiac histology FASEB bioAdvances Medium 35415460
2010 The transcription factor NRL directly binds the NRL-response element on the Ppp2r5c promoter (validated by EMSA and chromatin immunoprecipitation) and enhances Ppp2r5c transcriptional activity during mouse photoreceptor development. Electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), luciferase reporter assay The FEBS journal Medium 21078119
2026 PP2A-B56γ selectively dephosphorylates the ribosome biogenesis regulator Ebp1 at Ser335 in neurons exposed to polystyrene nanoplastics, reducing Ebp1 nucleolar localization, suppressing 47S pre-rRNA transcription, and inducing nucleolar stress that activates the p53/p21 pathway and promotes neuronal senescence. Pharmacological PP2A inhibition (LB-100) prevented these effects. In vitro dephosphorylation assay, mouse exposure model, immunofluorescence (Ebp1 nucleolar localization), pre-rRNA transcription assay, Western blot (p53/p21), pharmacological rescue with LB-100, co-culture system Free radical biology & medicine Medium 42097318
2025 De novo missense variants in PPP2R5C cause a neurodevelopmental disorder (Houge-Janssens syndrome spectrum). Variants affect either substrate binding, C-subunit binding, or both, and variably reduce catalytic activity of the phosphatase. Total loss-of-function variants can be inherited from non-symptomatic parents, indicating dominant-negative mechanism on substrate dephosphorylation is the likely pathogenic mechanism. Patient variant analysis, structural mapping onto PP2A crystal structure, PP2A catalytic activity assays, clinical phenotyping of 26 individuals American journal of human genetics Medium 39978342
2026 PPP2R5C (B56γ) interacts with Tau protein, reducing Tau levels and phosphorylation via ULK1-dependent autophagolysosomal activation and PP2A regulation. PPP2R5C reduction precedes Tau hyperphosphorylation in Tau Braak-staged brains. Co-immunoprecipitation, immunohistochemistry of staged brain tissue, exosome proteomics (LC-MS/MS), Western blot Cell reports. Medicine Low 41720088

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. The EMBO journal 134 17245430
2015 Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth. Human molecular genetics 75 25972378
1996 Assignment of human protein phosphatase 2A regulatory subunit genes b56alpha, b56beta, b56gamma, b56delta, and b56epsilon (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 --> p12. Genomics 58 8812429
2007 Serine 15 phosphorylation of p53 directs its interaction with B56gamma and the tumor suppressor activity of B56gamma-specific protein phosphatase 2A. Molecular and cellular biology 56 17967874
2004 Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown. Cancer research 48 15466190
2011 ATM-mediated phosphorylation activates the tumor-suppressive function of B56γ-PP2A. Oncogene 45 21460856
2010 A B56gamma mutation in lung cancer disrupts the p53-dependent tumor-suppressor function of protein phosphatase 2A. Oncogene 41 20473327
2014 The protein phosphatase 2A regulatory subunit B56γ mediates suppression of T cell receptor (TCR)-induced nuclear factor-κB (NF-κB) activity. The Journal of biological chemistry 37 24719332
2018 ER stress regulating protein phosphatase 2A-B56γ, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes. Cell death & disease 31 29988038
2014 The protein phosphatase 2A B56γ regulatory subunit is required for heart development. Developmental dynamics : an official publication of the American Association of Anatomists 31 24425002
2013 B56γ tumor-associated mutations provide new mechanisms for B56γ-PP2A tumor suppressor activity. Molecular cancer research : MCR 29 23723076
2020 Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ. Nature communications 27 33028863
2002 Genomic organization and mapping of the gene encoding the PP2A B56gamma regulatory subunit. Genomics 24 11863364
2011 Expression and distribution of PPP2R5C gene in leukemia. Journal of hematology & oncology 23 21548944
2010 Conserved and distinct modes of CREB/ATF transcription factor regulation by PP2A/B56gamma and genotoxic stress. PloS one 23 20730097
2002 Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma disrupts distal lung differentiation. American journal of physiology. Lung cellular and molecular physiology 22 12003782
2003 A truncated isoform of the protein phosphatase 2A B56gamma regulatory subunit may promote genetic instability and cause tumor progression. The American journal of pathology 21 12507892
2013 Proliferation inhibition and apoptosis induction of imatinib-resistant chronic myeloid leukemia cells via PPP2R5C down-regulation. Journal of hematology & oncology 19 24004697
2003 Localization of the PP2A B56gamma regulatory subunit at the Golgi complex: possible role in vesicle transport and migration. The American journal of pathology 19 12547706
2022 Protein phosphatase 2A-B56γ-Drp1-Rab7 signaling axis regulates mitochondria-lysosome crosstalk to sensitize the anti-cancer therapy of hepatocellular carcinoma. Biochemical pharmacology 17 35697120
2017 PP2A-B56γ is required for an efficient spindle assembly checkpoint. Cell cycle (Georgetown, Tex.) 16 28562161
2007 Liprin alpha1 interacts with PP2A B56gamma. Cell cycle (Georgetown, Tex.) 15 18235218
2022 Intracellular antibody targeting HBx suppresses invasion and metastasis in hepatitis B virus-related hepatocarcinogenesis via protein phosphatase 2A-B56γ-mediated dephosphorylation of protein kinase B. Cell proliferation 14 35811356
2023 Combined detection of SDC2/ADHFE1/PPP2R5C methylation in stool DNA for colorectal cancer screening. Journal of cancer research and clinical oncology 13 37270460
2021 Growth arrest of PPP2R5C and PPP2R5D double knockout mice indicates a genetic interaction and conserved function for these PP2A B subunits. FASEB bioAdvances 13 35415460
2012 HEAT repeat 1 motif is required for B56γ-containing protein phosphatase 2A (B56γ-PP2A) holoenzyme assembly and tumor-suppressive function. The Journal of biological chemistry 11 22315229
2004 A truncated isoform of the PP2A B56gamma regulatory subunit reduces irradiation-induced Mdm2 phosphorylation and could contribute to metastatic melanoma cell radioresistance. Histology and histopathology 11 15024700
2016 Activation of ERK/IER3/PP2A-B56γ-positive feedback loop in lung adenocarcinoma by allelic deletion of B56γ gene. Oncology reports 10 26986830
2003 Expression of the B56delta subunit of protein phosphatase 2A and Mea1 in mouse spermatogenesis. Identification of a new B56gamma subunit (B56gamma4) specifically expressed in testis. Cytogenetic and genome research 10 15051958
2024 LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA-DNA Triplex in Allergic Asthma. Allergy, asthma & immunology research 7 38262392
2022 A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility. Communications biology 6 36171301
2024 LincR-PPP2R5C regulates IL-1β ubiquitination in macrophages and promotes airway inflammation and emphysema in a murine model of COPD. International immunopharmacology 5 39018689
2010 Neural retina leucine-zipper regulates the expression of Ppp2r5c, the regulatory subunit of protein phosphatase 2A, in photoreceptor development. The FEBS journal 5 21078119
2022 Analysis of the Association of Two SNPs in the Promoter Regions of the PPP2R5C and SLC39A5 Genes with Litter Size in Yunshang Black Goats. Animals : an open access journal from MDPI 4 36290187
2025 Pathogenic de novo variants in PPP2R5C cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum. American journal of human genetics 3 39978342
2024 A micropeptide TREMP encoded by lincR-PPP2R5C promotes Th2 cell differentiation by interacting with PYCR1 in allergic airway inflammation. Allergology international : official journal of the Japanese Society of Allergology 3 39025723
2024 LincR-PPP2R5C Deficiency Alleviates Airway Remodeling by Inhibiting Epithelial-Mesenchymal Transition Through the PP2A/TGF-β1 Signaling Pathway in Chronic Experimental Allergic Asthma. Allergy, asthma & immunology research 2 39155740
2024 LincR-PPP2R5C deficiency enhancing the fungicidal activity of neutrophils in pulmonary cryptococcosis is linked to the upregulation of IL-4. mBio 2 39287443
2024 A recurrent variant in PPP2R5C identified in individuals with macrocephaly, intellectual disability, and seizures. HGG advances 2 39696819
2024 LincR-PPP2R5C regulates the PP2A signaling pathway in the macrophage-myofibroblast transition in a mouse model of epidural fibrosis. Molecular immunology 2 39729722
2026 Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer's disease. Cell reports. Medicine 1 41720088
2026 Polystyrene nanoplastics drive neuronal senescence via PP2A-B56γ-targeted p-Ebp1Ser335 dephosphorylation-mediated ribosome biogenesis dysfunction. Free radical biology & medicine 0 42097318
2025 Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for screening colorectal cancer in the Otog Front Banner. BMC gastroenterology 0 40307680
2022 [The Relationship between PPP2R5C and Molt-4 Cell Viability, HSP90-GR Signal in Childhood Acute T Lymphocytic Leukemia]. Zhongguo shi yan xue ye xue za zhi 0 35123608
2009 [Structural feature and biological function of PPP2R5C gene]. Zhongguo shi yan xue ye xue za zhi 0 19840435

Missed literature

Know a paper Affinage missed for PPP2R5C? Flag it for the maintainers and the community.

No submissions yet.