Affinage

PPM1G

Protein phosphatase 1G · UniProt O15355

Length
546 aa
Mass
59.3 kDa
Annotated
2026-06-10
30 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPM1G (PP2Cgamma) is a metal-dependent Ser/Thr protein phosphatase that originated as a constituent of the pre-mRNA splicing machinery and has since been resolved as a broadly acting nuclear and cytoplasmic regulator of RNA processing, transcription, translation, cell cycle, and innate immunity (PMID:9887102, PMID:17572683). In splicing it associates with the spliceosome throughout the reaction and is required during early A-complex assembly, with catalytic activity essential for function, and it engages YB-1 through a distinctive acidic domain that is itself regulated by reversible phosphorylation (PMID:9887102, PMID:17572683); it further dephosphorylates the SMN complex to maintain SMN stability and Cajal-body localization, and dephosphorylates the splicing factor SRSF3 to redirect alternative splicing (PMID:17984321, PMID:34290239). PPM1G couples DNA-damage signaling to transcription and the p53 axis: ATM-dependent dephosphorylation of USP7S at Ser18 destabilizes USP7S and Mdm2 to permit p53 accumulation, and ATM-regulated PPM1G binds 7SK RNA and Hexim1 to block P-TEFb reassembly into the inactive 7SK snRNP, sustaining NF-κB-driven RNA Pol II elongation—a coactivator role tuned by the ARF tumor suppressor (PMID:22361354, PMID:26324325, PMID:33288725). As a translational regulator it dephosphorylates 4E-BP1 at Thr37/46 and Ser65 and the cap-binding factor eIF4E, restraining cap-dependent translation and proliferation (PMID:23814053, PMID:39111820). It controls cell cycle progression by dephosphorylating and stabilizing p27Kip1 at Thr198 (PMID:27822412). PPM1G also operates as a holoenzyme with the PP2A regulatory subunit B56δ, which relocalizes it from nucleus to cytoplasm to dephosphorylate α-catenin at Ser641 and support adherens-junction assembly (PMID:31432583). In innate immunity PPM1G is a negative regulator that dephosphorylates the adaptors STING and MAVS and the transcription factor IRF7, dampening type-I interferon responses, an activity exploited by the KSHV protein ORF33 and the receptor CD97 (PMID:33219031, PMID:41774756). In vivo, PPM1G is essential for development and survival, with knockout mice showing embryonic lethality, neural tube and craniofacial defects, and elevated cell death under stress (PMID:23723158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established PPM1G's foundational identity by showing it is not merely a generic phosphatase but a bona fide spliceosomal factor whose catalytic activity drives early spliceosome assembly.

    Evidence Biochemical fractionation of HeLa nuclear extract with in vitro splicing reconstitution and active-site mutagenesis

    PMID:9887102

    Open questions at the time
    • The physiological splicing substrate(s) dephosphorylated were not identified
    • How phosphatase activity mechanistically promotes A complex formation unresolved
  2. 2007 High

    Defined the molecular interface for PPM1G's splicing function by linking it to YB-1 through a phosphorylation-regulated acidic domain, explaining how its activity is targeted to specific alternative splicing events.

    Evidence Reciprocal Co-IP, siRNA knockdown with CD44 v4/v5 splicing readout, in vitro phosphorylation, and acidic-domain mutagenesis

    PMID:17572683

    Open questions at the time
    • Kinase phosphorylating the acidic domain not identified
    • Mechanistic link between YB-1 binding and spliceosome assembly not detailed
  3. 2007 High

    Showed PPM1G regulates the SMN complex, connecting its phosphatase activity to Cajal-body integrity and SMN protein stability.

    Evidence siRNA knockdown, Co-IP, confocal immunofluorescence, and catalytically inactive mutant rescue

    PMID:17984321

    Open questions at the time
    • Specific SMN/Gemin3 phosphosites not mapped
    • Relationship to its spliceosomal role not integrated
  4. 2012 High

    Placed PPM1G within the DNA-damage response by showing it acts downstream of ATM to dephosphorylate USP7S, defining a phosphatase route to p53 activation.

    Evidence Co-IP, in vitro dephosphorylation assay, ionizing radiation, and siRNA knockdown with epistatic ordering

    PMID:22361354

    Open questions at the time
    • How ATM directs PPM1G specifically to USP7S not established
    • Direct vs indirect ATM-PPM1G regulation not resolved here
  5. 2013 High

    Identified PPM1G as a 4E-BP1 phosphatase, establishing a direct phosphatase input into cap-dependent translation, cell size, and protein content.

    Evidence Co-IP, in vitro phosphatase assay with purified PPM1G, siRNA knockdown, and cap-binding/cell-size readouts

    PMID:23814053

    Open questions at the time
    • Coordination with mTOR signaling timing only partially defined
    • Whether PPM1G is rate-limiting in vivo unclear
  6. 2013 High

    Demonstrated PPM1G is essential for organismal development and cell survival, establishing physiological importance beyond cell-based mechanism.

    Evidence Knockout mouse (embryonic lethal), zebrafish morpholino knockdown, and primary fibroblast survival/stress assays

    PMID:23723158

    Open questions at the time
    • Which substrate(s) underlie the developmental phenotype not identified
    • Tissue-specific requirements not dissected
  7. 2015 High

    Revealed a non-catalytic transcription-elongation role: PPM1G binds 7SK RNA and Hexim1 to block P-TEFb sequestration, sustaining NF-κB transcription after DNA damage under ATM control.

    Evidence RIP, Co-IP, ChIP, in vitro RNA binding, and ATM inhibitor treatment

    PMID:26324325

    Open questions at the time
    • Whether RNA binding requires phosphatase activity not resolved
    • Generality across NF-κB target genes not fully mapped
  8. 2016 High

    Connected PPM1G to cell cycle control via dephosphorylation and stabilization of p27Kip1 at T198, defining a G1/S checkpoint input and a localization effect on p27.

    Evidence Genomic phosphatase screen, Co-IP, in vitro dephosphorylation, FACS cell cycle analysis, and knockdown/overexpression

    PMID:27822412

    Open questions at the time
    • Interplay with the earlier p21/Rb cell-cycle observation not reconciled
    • How 14-3-3θ displacement is achieved mechanistically unclear
  9. 2019 High

    Reframed PPM1G as a holoenzyme by showing it partners with PP2A subunit B56δ, which relocalizes it to the cytoplasm to dephosphorylate α-catenin S641 and govern adherens-junction assembly.

    Evidence Co-IP, subcellular fractionation, in vitro dephosphorylation, α-catenin S641 mutagenesis, and migration assays

    PMID:31432583

    Open questions at the time
    • How B56δ reprograms substrate specificity at the structural level unknown
    • Scope of cytoplasmic substrates unlocked by B56δ not enumerated
  10. 2020 High

    Defined PPM1G as a negative regulator of innate immunity by dephosphorylating STING and MAVS, with KSHV ORF33 exploiting it for immunosuppression.

    Evidence Co-IP, phosphorylation assays, knockdown, viral infection, and interferon reporter assays

    PMID:33219031

    Open questions at the time
    • STING/MAVS phosphosites targeted not mapped here
    • Host-context regulation of PPM1G recruitment unclear
  11. 2020 Medium

    Showed the ARF tumor suppressor binds and tunes PPM1G's NF-κB coactivator function via a promoter-bound ternary complex, adding a regulatory layer to PPM1G transcription control.

    Evidence Co-IP, ChIP showing ternary complex at promoters, siRNA knockdown, and TNF stimulation

    PMID:33288725

    Open questions at the time
    • Whether ARF modulates PPM1G catalytic or scaffolding activity not resolved
    • Single-lab finding without reciprocal validation
  12. 2016 Medium

    Extended PPM1G's translational control role to glioblastoma, linking it to PI3K/AKT-dependent regulation of 4E-BP1 and downstream Id1 expression.

    Evidence siRNA knockdown, Co-IP, in vitro phosphatase assay, and PI3K/AKT inhibitor treatment

    PMID:27065332

    Open questions at the time
    • Largely confirmatory of the prior 4E-BP1 finding
    • Direct vs indirect PI3K control of PPM1G activity unresolved
  13. 2021 Medium

    Showed PPM1G dephosphorylates the splicing factor SRSF3 to remodel alternative splicing in hepatocellular carcinoma, broadening its RNA-processing substrate set.

    Evidence Co-IP, phosphorylation assay, RNA-seq splicing analysis, knockdown, and overexpression

    PMID:34290239

    Open questions at the time
    • SRSF3 phosphosites not mapped
    • Single-lab cancer-cell context
  14. 2023 Medium

    Identified MEK6 as a direct PPM1G substrate, placing PPM1G upstream of p38 MAPK signaling in lung adenocarcinoma.

    Evidence In vitro dephosphorylation assay, Co-IP, siRNA knockdown, and invasion/migration assays

    PMID:36349938

    Open questions at the time
    • MEK6 phosphosite dephosphorylated not specified
    • Single-lab finding
  15. 2024 Medium

    Showed PPM1G dephosphorylates eIF4E and harbors a 4E-BP-like binding motif, complementing its 4E-BP1 role to restrain cap-dependent translation and proliferation.

    Evidence Co-IP, in vitro dephosphorylation, eIF4E-binding motif analysis, and translational reporter/proliferation assays

    PMID:39111820

    Open questions at the time
    • Functional consequence of the 4E-BP-like motif on eIF4E sequestration unclear
    • Single-lab finding
  16. 2024 Medium

    Linked PPM1G to epigenetic regulation by showing it dephosphorylates and destabilizes TET1, impairing CLDN3 promoter demethylation and EMT in cholangiocarcinoma.

    Evidence Co-IP, in vitro dephosphorylation, bisulfite sequencing, knockdown, and EMT marker analysis

    PMID:39477806

    Open questions at the time
    • TET1 phosphosite not mapped
    • Single-lab finding
  17. 2024 Medium

    Confirmed and extended PPM1G's STING-suppressing role to macrophage M1 polarization in hepatic ischemia/reperfusion injury in vivo.

    Evidence Co-IP, p-STING western blot, knockdown, mouse hepatic I/R model, and macrophage polarization assay

    PMID:38372470

    Open questions at the time
    • Largely confirmatory of prior STING finding
    • Single-lab in vivo model
  18. 2025 Medium

    Showed PPM1G dephosphorylates NDR1 at Thr444 to suppress YAP S127 phosphorylation, driving YAP nuclear activity, stemness, and chemoresistance in triple-negative breast cancer.

    Evidence Co-IP, in vitro dephosphorylation, fractionation, Verteporfin epistasis, and in vitro/in vivo functional assays

    PMID:41072836

    Open questions at the time
    • How NDR1 dephosphorylation reduces YAP phosphorylation mechanistically unresolved
    • Single-lab finding
  19. 2025 Medium

    Extended the α-catenin axis in vivo, showing PPM1G maintains blood-testis barrier integrity in Sertoli cells through α/β-catenin localization and actin organization.

    Evidence siRNA, intratesticular injection, immunofluorescence, RNA-seq, and apoptosis assays in rat testes

    PMID:39952314

    Open questions at the time
    • Largely confirmatory of B56δ-α-catenin S641 finding
    • B56δ dependence in this tissue not tested
  20. 2025 Medium

    Added ferroptosis control to PPM1G's repertoire by showing it dephosphorylates and stabilizes GPX4, conferring cisplatin resistance in lung squamous cell carcinoma.

    Evidence siRNA knockdown, in vitro/in vivo tumor models, and GPX4 phosphorylation/stability assays

    PMID:42092080

    Open questions at the time
    • GPX4 phosphosite not mapped (abstract-level detail)
    • Single-lab finding
  21. 2026 Medium

    Showed the receptor CD97 recruits PPM1G to dephosphorylate IRF7 and block its nuclear translocation, defining a receptor-coupled mechanism for dampening type-I interferon and antiviral immunity.

    Evidence Co-IP, CD97 Arg-819/822 mutagenesis, IRF7 fractionation, viral replication assay, and CD97 knockout mice

    PMID:41774756

    Open questions at the time
    • IRF7 phosphosite not mapped
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single phosphatase achieves and switches between such diverse substrates and subcellular roles—beyond the B56δ holoenzyme relocalization mechanism—remains the central open question.
  • No structural model of substrate recognition
  • No systematic phosphosite/substrate map
  • Regulatory phosphorylation inputs (e.g., ATM, acidic domain) not unified into a control logic

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016787 hydrolase activity 4 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-73894 DNA Repair 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
4E-BP1B56ΔEIF4EHEXIM1SMNSTINGUSP7SYB-1
Complex memberships
7SK snRNP (via 7SK RNA/Hexim1 binding)PPM1G-B56δ (PP2A regulatory subunit) holoenzymespliceosome

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PP2Cgamma (PPM1G) is a pre-mRNA splicing factor physically associated with the spliceosome in vitro throughout the splicing reaction, first required during early spliceosome assembly for efficient A complex formation. Its phosphatase activity is required for splicing function, as an active-site mutant fails to support spliceosome assembly. PP2Cgamma localizes to the nucleus in vivo. Biochemical fractionation of HeLa nuclear extract, in vitro splicing reconstitution assay, active-site mutagenesis, nuclear localization by cell imaging Genes & development High 9887102
2007 PP2Cgamma (PPM1G) interacts with YB-1 via its distinctive acidic domain, which is essential for PP2Cgamma's activity in splicing regulation. PP2Cgamma is a phosphoprotein whose acidic domain is phosphorylated under splicing conditions in vitro; this phosphorylation enhances interaction with YB-1 and is reversed by PP2Cgamma in cis. PP2Cgamma knockdown inhibits cell proliferation and affects alternative splicing of CD44 exons v4 and v5, a YB-1 target. Co-immunoprecipitation, siRNA knockdown, in vitro phosphorylation assay, alternative splicing analysis by RT-PCR Nature structural & molecular biology High 17572683
2007 PPM1G/PP2Cgamma interacts with and dephosphorylates the SMN complex (SMN and Gemin3). PPM1G siRNA knockdown alters phosphorylation of SMN and Gemin3, causes loss of SMN from Cajal bodies, and reduces SMN stability. Overexpression of catalytically active, but not inactive, PPM1G restores SMN accumulation in Cajal bodies, demonstrating that phosphatase activity is required for SMN localization. siRNA knockdown, co-immunoprecipitation, immunofluorescence/confocal microscopy, overexpression of catalytically inactive mutant The Journal of cell biology High 17984321
2012 After ionizing radiation, ATM-dependent PPM1G dephosphorylates USP7S at serine 18 (a CK2 phosphorylation site), leading to USP7S downregulation, subsequent Mdm2 downregulation, and p53 accumulation. In unstressed cells, CK2 phosphorylates and stabilizes USP7S to maintain Mdm2 stabilization and p53 suppression. Co-immunoprecipitation, in vitro dephosphorylation assay, ionizing radiation treatment, siRNA knockdown, quantitative western blot Molecular cell High 22361354
2013 PPM1G binds to 4E-BP1 in cells and purified PPM1G dephosphorylates 4E-BP1 in vitro at Thr-37/46 and Ser-65 sites. PPM1G knockdown increases 4E-BP1 phosphorylation, slows 4E-BP1 dephosphorylation after amino acid starvation or mTOR inhibition, decreases 4E-BP1 association with the cap-dependent translation initiation complex, and increases cap-dependent translation rate, cell size, and protein content. Co-immunoprecipitation, in vitro phosphatase assay with purified PPM1G, siRNA knockdown, cap-binding assay, cell size measurement The Journal of biological chemistry High 23814053
2013 PPM1G is required for normal development and cell survival in vivo. ppm1g-/- mice are embryonic lethal after E12.5 with neural tube and craniofacial defects and increased cell death in neural epithelium. Loss of ppm1g in zebrafish causes neural defects. Primary ppm1g-/- fibroblasts fail to grow without immortalization, and immortalized knockout fibroblasts show increased cell death under oxidative and genotoxic stress. Knockout mouse model, zebrafish morpholino knockdown, primary fibroblast culture, cell death assays Developmental dynamics High 23723158
2014 PPM1G functions as a switch controlling WWP2 monomer versus WWP2/WWP1 heterodimer equilibrium. During cellular stress, WWP2 is inactivated (upregulating p73), while the WWP2-WWP1 complex remains intact to degrade ΔNp73, maintaining the balance between p73 and ΔNp73 levels. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, stress treatment Molecular and cellular biology Medium 25071155
2015 PPM1G (inducibly recruited by NF-κB to target promoters) directly binds 7SK RNA and the kinase inhibitor Hexim1 once P-TEFb has been released from the 7SK snRNP. This dual binding blocks P-TEFb reassembly onto the snRNP to sustain NF-κB-mediated RNA Pol II transcription elongation in response to DNA damage. ATM kinase regulates the PPM1G–7SK snRNP interaction through site-specific PPM1G phosphorylation. RNA immunoprecipitation (RIP), Co-IP, chromatin immunoprecipitation (ChIP), ATM inhibitor treatment, in vitro RNA-binding assay Molecular and cellular biology High 26324325
2016 PPM1G dephosphorylates p27Kip1 at T198. PPM1G interacts with p27 in cells and in vitro. Overexpression of PPM1G enhances p27 stability and delays cell cycle progression from G1 to S phase; PPM1G knockdown accelerates p27 degradation during G1 and renders cells resistant to serum deprivation-induced arrest. PPM1G inhibits the interaction of p27 with 14-3-3θ, and PPM1G knockdown promotes cytoplasmic mislocalization of p27. Genomic phosphatase screening, co-immunoprecipitation, in vitro dephosphorylation assay, cell cycle analysis (FACS), siRNA knockdown, overexpression American journal of cancer research High 27822412
2016 PPM1G activity modulates 4E-BP1 phosphorylation downstream of PI-3K/AKT signaling to regulate translational control of Id1 expression in glioblastoma cells. PPM1G knockdown increases 4E-BP1 phosphorylation and Id1 expression; PI-3K inhibition increases PPM1G phosphatase activity in vitro. PPM1G and 4E-BP1 co-associate in GBM cells. siRNA knockdown, co-immunoprecipitation, in vitro phosphatase assay, PI-3K/AKT inhibitor treatment Oncogene Medium 27065332
2006 Overexpression of PP2Cgamma (PPM1G) leads to S-phase accumulation coincident with proteasome-dependent degradation of p21WAF1/CIP1. The phosphatase activity of PP2Cgamma is required for reducing p21 protein levels. Phosphorylation of Rb is also reduced in cells expressing PP2Cgamma. Overexpression of wild-type and phosphatase-dead PP2Cgamma, cell cycle synchronization, proteasome inhibitor treatment, western blot FEBS letters Medium 17054950
2018 PPM1G overexpression downregulates HIF-1α protein under normoxic and acute hypoxic conditions via the proteasomal pathway. PPM1G-mediated HIF-1α degradation is dependent on prolyl hydroxylase (PHD) but independent of VHL. PPM1G deficiency upregulates endogenous HIF-1α under normoxic or acute oxidative stress conditions. Overexpression and knockdown of PPM1G, proteasome inhibitor treatment, PHD inhibitor treatment, western blot International journal of molecular sciences Medium 30081604
2019 PPM1G forms a holoenzyme complex with the PP2A regulatory subunit B56δ (first PPM-family member shown to act as a holoenzyme). B56δ promotes re-localization of PPM1G from nucleus to cytoplasm, enabling access to cytoplasmic substrates. The PPM1G-B56δ complex dephosphorylates α-catenin at serine 641, which is necessary for proper assembly of adherens junctions and prevention of aberrant cell migration. Co-immunoprecipitation, subcellular fractionation, in vitro dephosphorylation assay, site-directed mutagenesis of α-catenin S641, cell migration assay, siRNA knockdown EMBO reports High 31432583
2020 PPM1G dephosphorylates p-STING and p-MAVS to negatively regulate innate immune signaling. KSHV tegument protein ORF33 interacts with STING/MAVS and enhances recruitment of PPM1G to these adaptors for immunosuppression. PPM1G inhibition improves antiviral response against DNA and RNA viruses. Co-immunoprecipitation, phosphorylation assays, siRNA/shRNA knockdown, viral infection assays, interferon reporter assays Science advances High 33219031
2020 The ARF tumor suppressor binds PPM1G and negatively regulates its coactivator function in the NF-κB transcriptional circuit. ARF is stabilized upon binding PPM1G and forms a ternary complex with PPM1G and NF-κB at target gene promoters in a stimuli-dependent manner, tuning the magnitude and kinetics of NF-κB transcription. Loss of ARF leads to up-regulation of NF-κB antiapoptotic genes upon TNF stimulation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown, TNF stimulation, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 33288725
2021 PPM1G interacts with and dephosphorylates the splicing factor SRSF3 in hepatocellular carcinoma cells. PPM1G overexpression promotes dephosphorylation of SRSF3 and alters alternative splicing patterns of cell cycle and transcriptional regulation genes. Co-immunoprecipitation, phosphorylation assay, RNA-seq splicing analysis, siRNA knockdown, overexpression Cell death & disease Medium 34290239
2023 PPM1G dephosphorylates MEK6 (phospho-MEK6 identified as a direct substrate), thereby reducing downstream p38 MAPK phosphorylation and activation, contributing to proliferation, invasion, and metastasis of lung adenocarcinoma. In vitro dephosphorylation assay, co-immunoprecipitation, siRNA knockdown, western blot for p38 pathway, functional invasion/migration assays Carcinogenesis Medium 36349938
2024 PPM1G dephosphorylates eIF4E. PPM1G contains an eIF4E-binding motif similar to 4E-BPs. PPM1G inhibits cell proliferation by targeting phospho-eIF4E-dependent mRNA translation. Co-immunoprecipitation, in vitro dephosphorylation assay, eIF4E-binding motif analysis, cell proliferation assay, translational reporter assay Life science alliance Medium 39111820
2024 PPM1G dephosphorylates TET1, destabilizing TET1 protein and impairing its targeted demethylation of the CLDN3 promoter, thereby inhibiting epithelial-to-mesenchymal transition in cholangiocarcinoma. Co-immunoprecipitation, in vitro dephosphorylation assay, bisulfite sequencing, siRNA knockdown, EMT marker analysis Advanced science Medium 39477806
2024 PPM1G interacts with STING in macrophages (validated by co-immunoprecipitation) and dephosphorylates STING and its downstream components, suppressing inflammatory cytokine release and macrophage M1 polarization during hepatic ischemia/reperfusion injury. Co-immunoprecipitation, western blot for p-STING and downstream pathway components, siRNA/lentiviral knockdown, mouse hepatic ischemia/reperfusion model, macrophage polarization assay Immunity, inflammation and disease Medium 38372470
2025 PPM1G dephosphorylates α-catenin in Sertoli cells, maintaining blood-testis barrier function. Knockdown of ppm1g in rat testes compromises blood-testis barrier function, causes aberrant localization of α-catenin and β-catenin (mislocalized to cytoplasm instead of cell membrane), disrupts actin arrangement, reduces JAM2 expression, and induces Sertoli cell apoptosis. siRNA transfection, intratesticular injection, immunofluorescence, RNA sequencing, western blot, phospho-α-catenin analysis Molecular and cellular endocrinology Medium 39952314
2025 PPM1G interacts with NDR1 and dephosphorylates it at Thr444, which reduces YAP phosphorylation at Ser127, leading to YAP nuclear translocation and enhanced transcriptional activity, thereby promoting cancer stem cell-like properties and chemoresistance in triple-negative breast cancer. Co-immunoprecipitation, in vitro dephosphorylation assay, western blot for p-NDR1 and p-YAP, nuclear/cytoplasmic fractionation, YAP inhibitor (Verteporfin) treatment, in vitro and in vivo functional assays Pharmacological research Medium 41072836
2025 PPM1G suppresses ferroptosis in lung squamous cell carcinoma by dephosphorylating and stabilizing GPX4. PPM1G knockdown inhibits in vivo LUSC proliferation and enhances sensitivity to cisplatin. siRNA knockdown, in vitro and in vivo tumor models, phosphorylation and stability assays for GPX4, cisplatin sensitivity assay Scientific reports Medium 42092080
2026 CD97 interacts with PPM1G via its intracellular Arg-819 and Arg-822 residues. PPM1G then recruits and dephosphorylates IRF7, inhibiting its nuclear translocation and subsequent IFN-I activation, thereby dampening antiviral immunity and promoting viral replication. Co-immunoprecipitation, site-directed mutagenesis of CD97 (Arg-819/822), nuclear/cytoplasmic fractionation of IRF7, viral replication assay, CD97 knockout mice PLoS pathogens Medium 41774756
2025 PPM1G is a phosphatase of influenza nucleoprotein (NP) and is required for maintaining viral polymerase activity. Overexpression of PPM1G decreases viral replication. In ppm1g conditional knockout mice (ppm1g-flox/flox-Sftpc-Cre), lethal influenza infection led to survival and reduced lung viral loads, indicating PPM1G promotes vRNP replication by dephosphorylating NP to facilitate NP polymerization. Excess NP is degraded via the ATG7 autophagy-lysosome pathway. Affinity mass spectrometry (RdRp/vRNP-targeted), conditional KO mouse model, in vitro polymerase activity assay, NP phosphorylation assay, overexpression bioRxivpreprint Medium bio_10.1101_2025.09.18.676991

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Molecular cell 130 22361354
1999 The type 2C Ser/Thr phosphatase PP2Cgamma is a pre-mRNA splicing factor. Genes & development 78 9887102
2007 Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1. Nature structural & molecular biology 60 17572683
2020 PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion. Science advances 52 33219031
2015 Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis. The American journal of psychiatry 51 25982659
2007 Dephosphorylation of survival motor neurons (SMN) by PPM1G/PP2Cgamma governs Cajal body localization and stability of the SMN complex. The Journal of cell biology 49 17984321
2021 PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3. Cell death & disease 47 34290239
2015 PPM1G Binds 7SK RNA and Hexim1 To Block P-TEFb Assembly into the 7SK snRNP and Sustain Transcription Elongation. Molecular and cellular biology 41 26324325
2013 Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1). The Journal of biological chemistry 38 23814053
2016 Regulation of p27Kip1 phosphorylation and G1 cell cycle progression by protein phosphatase PPM1G. American journal of cancer research 37 27822412
2014 WWP2-WWP1 ubiquitin ligase complex coordinated by PPM1G maintains the balance between cellular p73 and ΔNp73 levels. Molecular and cellular biology 33 25071155
2013 Nuclear phosphatase PPM1G in cellular survival and neural development. Developmental dynamics : an official publication of the American Association of Anatomists 20 23723158
2020 The ARF tumor suppressor targets PPM1G/PP2Cγ to counteract NF-κB transcription tuning cell survival and the inflammatory response. Proceedings of the National Academy of Sciences of the United States of America 19 33288725
2019 PPM1G forms a PPP-type phosphatase holoenzyme with B56δ that maintains adherens junction integrity. EMBO reports 19 31432583
2016 Phosphatidylinositol-3 kinase-dependent translational regulation of Id1 involves the PPM1G phosphatase. Oncogene 15 27065332
2006 PP2Cgamma-mediated S-phase accumulation induced by the proteasome-dependent degradation of p21(WAF1/CIP1). FEBS letters 12 17054950
2024 PPM1G regulates hepatic ischemia/reperfusion injury through STING-mediated inflammatory pathways in macrophages. Immunity, inflammation and disease 9 38372470
2016 Functional interplay between PPM1G and the transcription elongation machinery. RNA & disease (Houston, Tex.) 9 27088130
2023 PPM1G promotes the progression of lung adenocarcinoma by inhibiting p38 activation via dephosphorylation of MEK6. Carcinogenesis 8 36349938
2018 The Protein Phosphatase PPM1G Destabilizes HIF-1α Expression. International journal of molecular sciences 6 30081604
2024 PPM1G Inhibits Epithelial-Mesenchymal Transition in Cholangiocarcinoma by Catalyzing TET1 Dephosphorylation for Destabilization to Impair Its Targeted Demethylation of the CLDN3 Promoter. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39477806
2024 PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1. Cellular signalling 4 39121976
2024 PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma. Cancer science 4 39462759
2024 PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation. Life science alliance 2 39111820
2020 Association of PPM1G methylation with risk-taking in alcohol use disorder. Scientific reports 2 32218500
2025 PPM1G dephosphorylates α-catenin to maintain the integrity of adherens junctions and regulates apoptosis in Sertoli cells. Molecular and cellular endocrinology 1 39952314
2025 Overexpression of PPM1G promotes cell metabolism and activates the NOTCH signaling pathway in lung adenocarcinoma. Translational lung cancer research 1 40799432
2026 The CD97-PPM1G axis dampens antiviral immunity by dephosphorylating IRF7 in type I interferon pathway. PLoS pathogens 0 41774756
2026 PPM1G suppresses ferroptosis in lung squamous cell carcinoma by dephosphorylating and stabilizing GPX4. Scientific reports 0 42092080
2025 PPM1G promotes chemoresistance in triple negative breast cancer by enhancing YAP signaling. Pharmacological research 0 41072836

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