Affinage

PPM1B

Protein phosphatase 1B · UniProt O75688

Length
479 aa
Mass
52.6 kDa
Annotated
2026-06-10
37 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

PPM1B is a metal ion-dependent (Mg2+/Mn2+), okadaic acid-insensitive serine/threonine protein phosphatase that broadly terminates phosphorylation-driven signaling by dephosphorylating activated kinases and transcriptional regulators (PMID:9684878, PMID:42094482). Catalysis proceeds through a trinuclear metal center in which a third metal ion coordinates the substrate phosphate for in-line hydrolysis (PMID:42094482). A dominant theme is the restraint of inflammatory and innate-immune signaling: PPM1B dephosphorylates IKKβ at Ser177/Ser181 to extinguish TNFα-induced NF-κB activation (PMID:18930133) and dephosphorylates TBK1 at Ser172 to limit IRF3-driven antiviral interferon responses (PMID:22750291). It also dephosphorylates RIP3 at Thr231/Ser232 to block MLKL recruitment and suppress necroptosis (PMID:25751141, PMID:33520691). Beyond immune control, PPM1B targets metabolic and growth regulators including AMPKα (an interaction requiring N-myristoylation at Gly2 for membrane association and physiological substrate recognition) (PMID:23088624), ULK1 to trigger autophagy upon release from a sequestering 14-3-3ε pool (PMID:36543144), DYRK1A at Ser258 to reduce downstream tau phosphorylation and aggregation (PMID:33380426), and several transcriptional regulators (PPARγ at Ser112/Ser273, p53-Ser366 as part of a GAS41 complex that confers substrate specificity, and Pax2 within the Groucho corepressor module) (PMID:23320500, PMID:21317290, PMID:25631048). PPM1B abundance and activity are themselves tightly controlled: PKA phosphorylation at Ser195 and the E3 ligases DCAF4L2-Cul4A-DDB1 and TRIM25 drive its proteasomal degradation, whereas the BRISC/ABRO1 complex stabilizes it via K63-linked deubiquitination at K326 in a YAP-coupled phase-separated assembly (PMID:23756813, PMID:27158335, PMID:39979355, PMID:39742393). Through these activities PPM1B functions as a tumor- and disease-relevant brake on NF-κB-driven cancer invasion, cell-cycle progression via CDK2, and diet-induced arterial stiffness through TGF-β–Smad signaling (PMID:27158335, PMID:39979355, PMID:39742393).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 Medium

    Established the basic biochemical identity of PPM1B as a phosphatase, answering whether the cloned gene product had catalytic activity and what cofactors it required.

    Evidence Recombinant human PP2Cβ expressed in E. coli assayed for cation dependence and okadaic acid sensitivity

    PMID:9684878

    Open questions at the time
    • No physiological substrate identified
    • No structural basis for catalysis defined
  2. 2008 High

    Identified IKKβ as a physiological substrate, defining PPM1B's role in terminating TNFα-induced NF-κB signaling rather than acting only on artificial substrates.

    Evidence Functional genomic screen, reciprocal Co-IP, gain/loss-of-function with NF-κB reporter and phospho-IKKβ readouts

    PMID:18930133

    Open questions at the time
    • No in vivo genetic confirmation in this study
    • Dynamics of TNFα-induced association not structurally defined
  3. 2011 High

    Demonstrated that a regulatory subunit (GAS41) confers substrate specificity, answering how PPM1B selects targets such as p53-Ser366 that it cannot dephosphorylate alone.

    Evidence Co-IP, in vitro dephosphorylation assay, UV-induced p53 phosphorylation and cell survival readouts

    PMID:21317290

    Open questions at the time
    • Structural basis for GAS41-conferred specificity unknown
    • Generality of subunit-directed targeting to other substrates not established
  4. 2012 High

    Extended PPM1B's immune-regulatory role to antiviral signaling by identifying TBK1-Ser172 as a substrate, using a phosphatase-dead mutant to prove catalytic dependence.

    Evidence In vitro dephosphorylation, R179G active-site mutant, viral infection assays, siRNA with IRF3/IFNβ readouts

    PMID:22750291

    Open questions at the time
    • In vivo relevance to antiviral defense not tested
    • Recruitment mechanism to TBK1 undefined
  5. 2012 Medium

    Revealed context-dependent transcriptional regulation through EKLF/KLF1, complicating a purely repressive model.

    Evidence Co-IP via PEST1 sequence, promoter-reporter with phosphatase-dead mutant, shRNA in CD34+ cells

    PMID:22393050

    Open questions at the time
    • Opposite outcomes across assay systems unresolved
    • Direct EKLF dephosphorylation site not mapped
  6. 2013 High

    Showed N-myristoylation is required for physiological substrate recognition (AMPKα) rather than catalysis itself, explaining membrane targeting of an otherwise soluble phosphatase.

    Evidence N-myristoylation assay, G2A mutant, membrane fractionation, in vitro assays with AMPKα and PNPP

    PMID:23088624

    Open questions at the time
    • Which membranes PPM1B associates with not defined
    • Whether myristoylation gates other substrates untested
  7. 2013 High

    Expanded PPM1B into transcriptional/metabolic control by identifying nuclear PPARγ dephosphorylation in adipocytes.

    Evidence IP-MS, in vitro dephosphorylation, nuclear localization, knockdown in 3T3-L1 with transcriptional readout

    PMID:23320500

    Open questions at the time
    • In vivo metabolic consequence not tested
    • Relative contribution of Ser112 vs Ser273 unclear
  8. 2013 Medium

    Identified PKA-Ser195 phosphorylation as a degradation switch, answering how upstream signaling can inactivate PPM1B to license inflammation.

    Evidence Serine mutagenesis, PKA kinase assay, proteasome inhibitor and H89 experiments, stability immunoblotting

    PMID:23756813

    Open questions at the time
    • Responsible E3 ligase not identified in this study
    • Single lab, no in vivo validation
  9. 2015 High

    Defined PPM1B as the RIP3 phosphatase that suppresses necroptosis, establishing a direct cell-death control function validated in vivo.

    Evidence Co-IP, in vitro dephosphorylation of Thr231/Ser232, Ppm1b-deficient mice with TNF challenge

    PMID:25751141 PMID:33520691

    Open questions at the time
    • Regulation of PPM1B–RIP3 association dynamics incomplete
    • Tissue-specific necroptosis contributions not mapped
  10. 2015 High

    Showed PPM1B acts within the Groucho/Pax2 corepressor complex to switch a transcriptional activator to a repressor, linking phosphatase activity to chromatin state.

    Evidence Co-IP, ChIP, loss-of-function with gene expression and H3K4 methylation readouts

    PMID:25631048

    Open questions at the time
    • Pax2 dephosphorylation site not precisely mapped
    • Generality to other Groucho-recruited factors unknown
  11. 2016 Medium

    Identified DCAF4L2-Cul4A-DDB1 as an E3 ligase degrading PPM1B, mechanistically connecting PPM1B loss to NF-κB-driven cancer invasion.

    Evidence MS of E3 complex, Co-IP, knockdown/overexpression with invasion assay and NF-κB readout

    PMID:27158335

    Open questions at the time
    • Ubiquitination site on PPM1B not mapped
    • In vivo metastasis dependence on PPM1B not fully isolated
  12. 2018 Medium

    Placed PPM1B as a negative regulator of the p38-RB1-E2F1 growth axis, linking it to proliferation control.

    Evidence shRNA knockdown in U2OS, phospho-RB1 immunoblotting, E2F1 target qRT-PCR, bleomycin sensitivity

    PMID:29654756

    Open questions at the time
    • Direct substrate in the pathway not identified
    • Single lab, single cell line
  13. 2021 High

    Linked PPM1B to neurodegeneration-relevant signaling by showing it dephosphorylates DYRK1A-Ser258 to reduce tau hyperphosphorylation and aggregation.

    Evidence LC-MS/MS interaction mapping, Co-IP, in vitro dephosphorylation, tau phosphorylation/aggregation in HEK293

    PMID:33380426

    Open questions at the time
    • No in vivo or neuronal model
    • Relevance to disease tauopathies not established
  14. 2022 Medium

    Resolved how PPM1B activity is gated spatially, showing 14-3-3ε sequesters PPM1B until leucine deprivation triggers crotonylation-driven release to dephosphorylate ULK1 and initiate autophagy.

    Evidence Crotonylome profiling, MD simulation, Co-IP, crotonylation-deficient mutant, autophagy and ULK1 phospho readouts

    PMID:36543144

    Open questions at the time
    • ULK1 dephosphorylation site not mapped
    • In vivo autophagic relevance untested
  15. 2023 Medium

    Identified a regulatory inhibitor (TXLNA) that blocks PPM1B–TBK1 binding, explaining aberrant TBK1 activation in cancer.

    Evidence BioID and APEX2 proximity proteomics, Co-IP, phospho-TBK1 immunoblotting

    PMID:37506885

    Open questions at the time
    • Structural basis of competition unknown
    • In vivo tumor relevance not tested
  16. 2023 Medium

    Defined a PPM1B–RBM10–YBX1 triple complex in which RBM10 scaffolds YBX1 dephosphorylation, controlling YBX1 nuclear translocation and tumorigenesis.

    Evidence Co-IP of triple complex, phospho-immunoblotting, nuclear fractionation, xenograft rescue

    PMID:38246397

    Open questions at the time
    • YBX1 phospho-site not mapped here
    • Scaffolding stoichiometry undefined
  17. 2024 Medium

    Mapped a specific YBX1-Ser314 dephosphorylation event that destabilizes YBX1 via USP10-coupled ubiquitination, controlling chemoresistance and PANoptosis in gastric cancer.

    Evidence Co-IP, S314 mutagenesis, ubiquitination assays, cell death and oxaliplatin resistance assays

    PMID:38364962

    Open questions at the time
    • No in vitro reconstitution of dephosphorylation
    • Mechanistic link to USP10 indirect
  18. 2025 High

    Established BRISC/ABRO1-mediated K63 deubiquitination at K326 as a stabilizing regulation, demonstrating in vivo protection against diet-induced arterial stiffness through TGF-β–Smad signaling.

    Evidence siRNA screen, MS, GST pull-down, Co-IP, phase-separation assays, smooth muscle-specific knockout mice, Doppler/telemetry

    PMID:39742393

    Open questions at the time
    • Phosphatase substrate driving arterial phenotype not pinpointed
    • Mechanism of YAP-dependent phase separation incomplete
  19. 2025 Medium

    Identified TRIM25 as a further E3 ligase degrading PPM1B, placing it upstream of CDK2 in a cell-cycle control axis with in vivo tumor suppression.

    Evidence Co-IP, ubiquitination assay, overexpression/knockout with cell cycle and proliferation readouts, in vivo tumor growth

    PMID:39979355

    Open questions at the time
    • Whether CDK2 is a direct PPM1B substrate not reconstituted here
    • Ubiquitination site not mapped
  20. 2025 Medium

    Provided structural mechanism: PPM1B uses a trinuclear metal architecture in which the third metal coordinates substrate phosphate for in-line hydrolysis, convergent with the PPP arginine clamp.

    Evidence Structural/biochemical study of M3 catalytic role (preprint)

    PMID:42094482

    Open questions at the time
    • Preprint, not peer reviewed
    • How substrate-specific contacts integrate with the core mechanism unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PPM1B's many reported substrates are prioritized in vivo and which dephosphorylation events drive its tissue-specific roles in inflammation, metabolism, cancer, and vascular biology.
  • No unified substrate-targeting code beyond GAS41/RBM10 scaffolds
  • Limited in vivo substrate-resolution genetics
  • Several substrate claims rest on single-lab Co-IP without reconstitution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
DYRK1AGAS41IKBKBPPARGRIPK3TBK1YBX1YWHAE
Complex memberships
BRISC/ABRO1 complexGAS41-PPM1B complexGroucho4 repressor complexRBM10-YBX1-PPM1B complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 PPM1B (Ppm1b) acts as a direct phosphatase for RIP3 (receptor-interacting protein 3), dephosphorylating its Thr231 and Ser232 auto-phosphorylation sites. This dephosphorylation prevents recruitment of MLKL to the necrosome, thereby suppressing necroptosis both in cultured cells and in vivo (Ppm1b-deficient mice showed enhanced TNF-induced death and elevated RIP3 phosphorylation in a RIP3-dependent manner). Co-immunoprecipitation, in vitro dephosphorylation assay, Ppm1b-deficient mouse model with TNF challenge, phospho-specific immunoblotting Nature cell biology High 25751141
2008 PPM1B (and PPM1A) function as IKKβ phosphatases, dephosphorylating IKKβ at Ser177 and Ser181 to terminate TNFα-induced NF-κB activation. PPM1B associates with the phosphorylated form of IKKβ, and this interaction is transiently induced by TNFα. Knockdown of PPM1B enhances TNFα-induced IKKβ phosphorylation, NF-κB nuclear translocation, and NF-κB-dependent gene expression. Functional genomic screen, co-immunoprecipitation, overexpression/knockdown, NF-κB reporter assay, immunoblotting for phospho-IKKβ Cellular signalling High 18930133
2012 PPM1B acts as a TBK1 phosphatase, dephosphorylating TBK1 at Ser172 both in vivo and in vitro. PPM1B wild-type but not its phosphatase-deficient R179G mutant inhibits TBK1-mediated antiviral signaling and facilitates VSV replication. Viral infection induces transient association of PPM1B with TBK1. Knockdown of PPM1B enhances virus-induced IRF3 phosphorylation and IFNβ production. Functional genomics, in vitro dephosphorylation assay, phosphatase-dead mutant (R179G), co-immunoprecipitation, viral infection assay, siRNA knockdown with IRF3/IFNβ readouts Cellular signalling High 22750291
2013 PPM1B is N-myristoylated (at Gly2), and this modification is essential for its ability to dephosphorylate AMPKα in cells. The non-myristoylated G2A mutant prevents membrane association and shows reduced activity toward AMPKα in vitro, though it retains higher specific activity against an artificial substrate (PNPP), suggesting N-myristoylation is required for physiological substrate recognition rather than catalysis per se. N-myristoylation assay, G2A mutant analysis, membrane fractionation, in vitro phosphatase assay with AMPKα and PNPP The Biochemical journal High 23088624
2013 PPM1B directly interacts with and dephosphorylates PPARγ at Ser112 (and Ser273), increasing PPARγ-mediated transcription. Endogenous PPM1B is localized in the nucleus of mature adipocytes where it binds PPARγ. Knockdown of PPM1B blunts expression of some PPARγ target genes. Immunoprecipitation coupled to tandem MS, in vitro dephosphorylation assay, nuclear localization by fractionation/immunofluorescence, knockdown in 3T3-L1 adipocytes with transcriptional readout The Biochemical journal High 23320500
2011 The GAS41–PP2Cβ (PPM1B) complex, but not PPM1B alone, specifically dephosphorylates p53 at Ser366, reducing UV-induced p53 stabilization and increasing cell survival after genotoxic damage. GAS41 acts as a regulatory subunit controlling substrate specificity of PPM1B. Co-immunoprecipitation, in vitro dephosphorylation assay, ectopic expression, UV irradiation with p53 phosphorylation readout, cell survival assay The Journal of biological chemistry High 21317290
2015 PPM1B is an essential component of the Groucho4 repressor complex recruited by Pax2 to chromatin. PPM1B dephosphorylates the Pax2 activation domain, displacing the adaptor PTIP, thereby inhibiting H3K4 methylation and switching Pax2 from a transcriptional activator to a repressor. Loss of PPM1B prevents Groucho-mediated gene repression. Co-immunoprecipitation, chromatin immunoprecipitation, loss-of-function (PPM1B knockout/depletion) with gene expression and histone methylation readouts The Journal of biological chemistry High 25631048
2012 PPM1B interacts with EKLF (KLF1) via the EKLF PEST1 sequence. PPM1B superactivates EKLF at the β-globin and BKLF promoters in an erythroid cell line, dependent on intact PPM1B phosphatase activity. Conversely, depletion of PPM1B in CD34+ cells leads to higher endogenous β-globin gene activation after differentiation, indicating a complex, context-dependent regulatory role. Co-immunoprecipitation, promoter-reporter assay, PPM1B phosphatase-dead mutant, shRNA knockdown in CD34+ cells with gene expression readout The Journal of biological chemistry Medium 22393050
2013 PKA phosphorylates PPM1B (PP2Cβ) at Ser195, promoting its ubiquitin-dependent proteasomal degradation and thereby activating NF-κB-mediated inflammatory signaling. PKA inhibition (by H89) stabilizes PPM1B and restores its anti-inflammatory function. Mutagenesis of serine residues, PKA kinase assay, proteasome inhibitor experiments, H89 PKA inhibitor, immunoblotting for PPM1B stability and NF-κB pathway Biochemical and biophysical research communications Medium 23756813
2021 PPM1B directly dephosphorylates DYRK1A at Ser258 (a DYRK1A autophosphorylation site), thereby inhibiting DYRK1A kinase activity. PPM1B-mediated dephosphorylation of DYRK1A subsequently reduces tau phosphorylation at Thr212 and inhibits toxic tau oligomerization and aggregation. LC-MS/MS identification of DYRK1A-PPM1B interaction, Co-immunoprecipitation, in vitro dephosphorylation assay, tau phosphorylation and aggregation readouts in HEK293 cells The Journal of biological chemistry High 33380426
2022 PPM1B is sequestered by 14-3-3ε under basal conditions; leucine deprivation induces crotonylation of 14-3-3ε (regulated by HDAC7), disrupting the 14-3-3ε amphipathic pocket and releasing PPM1B. Free PPM1B then dephosphorylates ULK1, initiating autophagy. Crotonylome profiling, molecular dynamics simulation, co-immunoprecipitation, 14-3-3ε crotonylation-deficient mutant, autophagy assays, ULK1 phosphorylation immunoblotting Cell reports Medium 36543144
2016 PPM1B is a substrate of the Cul4A-DDB1-DCAF4L2 E3 ubiquitin ligase complex; DCAF4L2 overexpression promotes PPM1B degradation, leading to NF-κB pathway activation and increased colorectal cancer invasion and metastasis. Knockdown of PPM1B abrogates the shDCAF4L2-mediated inhibition of cell invasion. Mass spectrometry identification of E3 complex components, co-immunoprecipitation, knockdown/overexpression with invasion assay, immunoblotting for NF-κB American journal of translational research Medium 27158335
2024 PPM1B directly interacts with YBX1 and dephosphorylates YBX1 at Ser314. This dephosphorylation affects USP10-mediated deubiquitination of YBX1, reducing YBX1 protein stability, which suppresses PANoptosis inhibition and decreases oxaliplatin resistance in gastric cancer cells. Co-immunoprecipitation, overexpression/silencing experiments, phosphorylation site mutagenesis (S314), ubiquitination assays, cell death and drug resistance assays Cancer letters Medium 38364962
2023 TXLNA interacts with TBK1 and impairs PPM1B binding to TBK1, thereby inhibiting PPM1B-mediated dephosphorylation of TBK1 at Ser172 and contributing to aberrant TBK1 activation in cancer cells. BioID biotinylation with TMT quantitative proteomics, APEX2 proximity labeling with TMT proteomics, co-immunoprecipitation, phospho-TBK1 immunoblotting Biochimica et biophysica acta. Molecular cell research Medium 37506885
2025 TRIM25 physically interacts with PPM1B and promotes its ubiquitin-dependent degradation, leading to increased CDK2 phosphorylation and gastric cancer cell proliferation. PPM1B overexpression induces G1 phase cell cycle arrest and suppresses tumor growth, placing PPM1B upstream of CDK2 in the TRIM25/PPM1B/CDK2 signaling axis. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown/knockout with cell cycle and proliferation readouts, in vivo tumor growth assay Scientific reports Medium 39979355
2025 BRISC complex component ABRO1 directly binds YAP and undergoes liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, promoting K63-linked deubiquitination of PPM1B at K326. Smooth muscle cell-specific PPM1B overexpression attenuates high-fat/high-sucrose diet-induced arterial stiffness in a K326 K63-polyubiquitination-dependent manner. ABRO1 or BRCC3 knockout attenuates arterial stiffness and TGF-β–Smad signaling activation. siRNA screening, mass spectrometry, GST pull-down, co-immunoprecipitation, protein purification, immunofluorescence, Doppler ultrasound, telemetry, smooth muscle cell-specific knockout mice Circulation research High 39742393
2023 PPM1B forms a triple complex with RBM10 and YBX1, in which PPM1B serves as the phosphatase for YBX1. RBM10 knockdown attenuates the YBX1–PPM1B association, elevating YBX1 phosphorylation and nuclear translocation; these tumorigenic phenotypes are reversed by PPM1B overexpression. Co-immunoprecipitation (triple complex), phosphorylation immunoblotting, overexpression/knockdown, nuclear-cytoplasmic fractionation, xenograft rescue experiment Experimental cell research Medium 38246397
2021 Ppm1b negatively regulates 3-bromopyruvate (3-BP)-induced necroptosis in breast cancer cells through dephosphorylation of RIP3, consistent with the established Ppm1b–RIP3 phosphatase relationship. Immunoblotting for phospho-RIP3, cell viability assay, overexpression/knockdown, mouse xenograft model Frontiers in oncology Medium 33520691
1998 Recombinant human PP2Cβ (PPM1B) expressed in E. coli exhibits metal ion-dependent (Mg2+/Mn2+) serine/threonine phosphatase activity that is insensitive to okadaic acid, similar to PP2Cα. Cloning from human liver cDNA library, recombinant protein expression in E. coli, phosphatase activity assay with cation dependence and okadaic acid inhibition tests FEBS letters Medium 9684878
2020 In Clostridium difficile toxin B (TcdB)-induced colonic inflammation, PPM1B expression is transcriptionally regulated by the AKT/FOXO3 signaling pathway; PPM1B acts as a key mediator promoting phosphorylation of NF-κB p65 and pro-inflammatory cytokine production. Dual-luciferase reporter assay, chromatin immunoprecipitation, lentiviral overexpression/knockdown, ELISA for cytokines, mouse model with PI3K/AKT inhibitor American journal of translational research Low 33194024
2018 PPM1B depletion in U2OS cells suppresses cell growth accompanied by hyper-phosphorylation of RB1 and up-regulation of E2F1 target genes (p27 and caspase 7), placing PPM1B as a negative regulator of the p38-RB1-E2F1 pathway. PPM1B depletion also sensitizes cells to bleomycin-induced cell death. Lentiviral shRNA knockdown, immunoblotting for phospho-RB1, qRT-PCR for E2F1 targets, colony/proliferation assay, bleomycin cell death assay Biochemical and biophysical research communications Medium 29654756
2020 HN252, a p-terphenyl derivative, was identified as a potent PPM1B inhibitor (Ki = 0.52 µM). Using this inhibitor, five proteins were validated as PPM1B substrates by immunoprecipitation: CDK2 (known) and AKT1, HSP90B, β-catenin, and BRCA1 (novel). In vitro phosphatase inhibition assay (Ki determination), cellular target engagement, immunoprecipitation validation of phosphorylated substrates Journal of cellular and molecular medicine Medium 33048454
2025 PPM1B utilizes a trinuclear metal (Mg2+/Mn2+) architecture for phosphatase activity. The third metal ion (M3) directly coordinates the substrate phosphate, positioning it for in-line SN2 hydrolysis, and also positions a water molecule to protonate the departing alkoxide. This M3 function is mechanistically convergent with the arginine clamp in phosphoprotein phosphatases (PPP), but achieved through a fundamentally different catalytic architecture. Structural/biochemical studies of PPM1B in the context of Pseudomonas aeruginosa infection; trinuclear metal center characterized; functional studies of M3 role in catalysis (preprint) bioRxivpreprint Medium 42094482
2025 In lung cancer cells, decreased PPM1B expression leads to increased inhibitory phosphorylation of MYPT1 (regulatory subunit of myosin phosphatase) at Thr853, which activates PRMT5 (via phospho-Thr80), resulting in symmetric dimethylation of histone H2A and decreased retinoblastoma protein expression, driving tumor progression. Western blotting, PCR, immunohistochemistry in patient tissues; correlation of PPM1B loss with MYPT1 phospho-Thr853, PRMT5 phospho-Thr80, and H2A symmetric dimethylation levels Biomolecules Low 41301499
2024 YAP regulates PPM1B ubiquitination and nuclear translocation in astrocytes; knockdown of PPM1B in astrocytes inhibits TGF-β signaling. Icariin treatment inhibits YAP, thereby affecting PPM1B ubiquitination and nuclear translocation to suppress reactive astrocyte activation. Immunoprecipitation-Western blot for ubiquitination, cytoplasm-nuclear separation fractionation, PPM1B knockdown with TGF-β signaling readout Frontiers in pharmacology Low 39439899
2014 PPM1B depletion induces premature senescence in IMR-90 fibroblasts, with senescence partially rescued by p38 MAPK inactivation, identifying PPM1B as a regulator of both p38 MAPK-dependent and p38 MAPK-independent senescence pathways. Lentiviral shRNA knockdown, senescence markers (β-galactosidase, growth arrest), p38 MAPK inhibitor rescue Mechanisms of ageing and development Medium 24674756

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Ppm1b negatively regulates necroptosis through dephosphorylating Rip3. Nature cell biology 134 25751141
2008 PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cellular signalling 94 18930133
2012 PPM1B negatively regulates antiviral response via dephosphorylating TBK1. Cellular signalling 63 22750291
2024 Modulation of YBX1-mediated PANoptosis inhibition by PPM1B and USP10 confers chemoresistance to oxaliplatin in gastric cancer. Cancer letters 49 38364962
2013 N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells. The Biochemical journal 43 23088624
2016 DCAF4L2 promotes colorectal cancer invasion and metastasis via mediating degradation of NFκb negative regulator PPM1B. American journal of translational research 35 27158335
2013 The serine/threonine phosphatase PPM1B (PP2Cβ) selectively modulates PPARγ activity. The Biochemical journal 34 23320500
2015 miR-186 downregulates protein phosphatase PPM1B in bladder cancer and mediates G1-S phase transition. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 26494000
2011 The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability. The Journal of biological chemistry 29 21317290
2015 The Groucho-associated phosphatase PPM1B displaces Pax transactivation domain interacting protein (PTIP) to switch the transcription factor Pax2 from a transcriptional activator to a repressor. The Journal of biological chemistry 27 25631048
1998 The cloning expression and tissue distribution of human PP2Cbeta. FEBS letters 26 9684878
2022 Lysine crotonylation regulates leucine-deprivation-induced autophagy by a 14-3-3ε-PPM1B axis. Cell reports 23 36543144
2020 Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway. Journal of immunology research 23 32908938
2021 Protein phosphatase PPM1B inhibits DYRK1A kinase through dephosphorylation of pS258 and reduces toxic tau aggregation. The Journal of biological chemistry 21 33380426
2018 Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis. Journal of cellular biochemistry 20 30269354
2012 Functional interactions between erythroid Krüppel-like factor (EKLF/KLF1) and protein phosphatase PPM1B/PP2Cβ. The Journal of biological chemistry 19 22393050
2023 A comprehensive overview of PPM1B: From biological functions to diseases. European journal of pharmacology 16 36863552
2021 Exosomal miR-181a-5p reduce Mycoplasma gallisepticum (HS strain) infection in chicken by targeting PPM1B and activating the TLR2-mediated MyD88/NF-κB signaling pathway. Molecular immunology 16 34715577
2023 Pleckstrin-2-promoted PPM1B degradation plays an important role in transforming growth factor-β-induced breast cancer cell invasion and metastasis. Cancer science 12 36928924
2014 PPM1B depletion induces premature senescence in human IMR-90 fibroblasts. Mechanisms of ageing and development 12 24674756
2013 PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling. Biochemical and biophysical research communications 12 23756813
2020 Identification of HN252 as a potent inhibitor of protein phosphatase PPM1B. Journal of cellular and molecular medicine 11 33048454
2018 PPM1B depletion in U2OS cells supresses cell growth through RB1-E2F1 pathway and stimulates bleomycin-induced cell death. Biochemical and biophysical research communications 10 29654756
2023 Circ_0006251 mediates the proliferation and apoptosis of vascular smooth muscle cells in CAD via enhancing TET3 and PPM1B expression. Cellular and molecular biology (Noisy-le-Grand, France) 6 37715433
2024 Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes. Frontiers in pharmacology 5 39439899
2019 A heterozygous deficiency in protein phosphatase Ppm1b results in an altered ovulation number in mice. Molecular medicine reports 5 31059097
2025 BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness. Circulation research 4 39742393
2025 PPM1B degradation mediated by TRIM25 ubiquitination modulates cell cycle and promotes gastric cancer growth. Scientific reports 4 39979355
2023 Overexpression of PPM1B inhibited chemoresistance to temozolomide and proliferation in glioma cells. Cell biology international 4 37798941
2020 Clostridium difficile toxin B-induced colonic inflammation is mediated by the FOXO3/PPM1B pathway in fetal human colon epithelial cells. American journal of translational research 4 33194024
2024 RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities. Experimental cell research 3 38246397
2021 [TRIM59 regulates invasion and migration of nasopharyngeal carcinoma cells by targeted modulation of PPM1B]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 34308852
2023 TXLNA enhances TBK1 phosphorylation by suppressing PPM1B recruitment. Biochimica et biophysica acta. Molecular cell research 2 37506885
2023 Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis. Molecular and cellular biochemistry 2 37515673
2021 Ppm1b Negatively Regulates 3-Bromopyruvate Induced Necroptosis in Breast Cancer Cells. Frontiers in oncology 2 33520691
2026 PPM1B utilizes a trinuclear metal architecture for phosphatase activity. bioRxiv : the preprint server for biology 0 42094482
2025 Decreased PPM1B Expression Drives PRMT5-Mediated Histone Modification in Lung Cancer Progression. Biomolecules 0 41301499

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