Affinage

PPP1CC

Serine/threonine-protein phosphatase PP1-gamma catalytic subunit · UniProt P36873

Length
323 aa
Mass
37.0 kDa
Annotated
2026-06-10
40 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP1CC encodes PP1γ, a serine/threonine protein phosphatase catalytic subunit whose specificity and subcellular targeting are dictated by interchangeable regulatory/scaffold partners, allowing it to act at distinct cell-cycle, signaling, and developmental nodes (PMID:12529430, PMID:21723128). Across the mammalian cell cycle PP1γ dynamically relocalizes from nucleoli through kinetochores and chromosomes to the cleavage furrow (PMID:12529430), and its association with mitotic chromatin via the Repo-Man regulatory subunit is reversed by Aurora B phosphorylation to sustain the mitotic chromatin phosphorylation state (PMID:32938714). At centrosomes it is recruited through Mst2 into a Nek2A–PP1γ complex that opposes centrosome disjunction, an assembly blocked by Plk1 phosphorylation of Mst2 (PMID:21723128), and in meiotic prophase NEK1-phosphorylated PP1γ dephosphorylates WAPL to drive cohesin removal (PMID:27760328). PP1γ also dephosphorylates targeted substrates in diverse pathways: it is released from inhibitory mitochondrial URI complexes by S6K1 phosphorylation to set up an apoptotic negative-feedback loop (PMID:17936702), is recruited by PPP1R3G to dephosphorylate RIPK1 and license apoptosis/necroptosis (PMID:34862394), dephosphorylates CREB-Ser133 within an HDAC1 complex during dopaminergic neurodegeneration (PMID:35501151), and dephosphorylates YAP to control Hippo-dependent trophectoderm specification and tumor progression (PMID:41403070, PMID:40626009). Additional substrate/partner relationships place PP1γ in SMN complex assembly via Gemin8 (PMID:22454514), ERK suppression via hScrib (PMID:23359326), and neuronal insulin signaling via AKT2 (PMID:37085815). The gene generates two alternatively spliced isoforms, PP1γ1 and PP1γ2, both catalytically active (PMID:8394140, PMID:9339378); the testis-enriched PP1γ2 is indispensable for spermiogenesis, with knockout mice showing chromatin condensation, acrosome, and flagellar defects and male infertility (PMID:17301292, PMID:20385779, PMID:24089200).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1993 High

    Establishing that PPP1CC is a distinct PP1 gene generating two C-terminally divergent isoforms defined the molecular substrate for all later isoform-specific biology.

    Evidence cDNA cloning from a human teratocarcinoma library and chromosomal mapping by somatic cell hybrid and FISH analysis

    PMID:8394140

    Open questions at the time
    • Did not establish functional differences between PP1γ1 and PP1γ2
    • No tissue-specific expression pattern defined
  2. 1997 Medium

    Demonstrating both isoforms are catalytically competent confirmed that alternative splicing alters targeting rather than abolishing phosphatase activity.

    Evidence Complementation of the fission yeast dis2-11 cold-sensitive PP1 mutant

    PMID:9339378

    Open questions at the time
    • Yeast complementation does not reveal mammalian substrate specificity
    • Does not address isoform-specific regulatory partners
  3. 2003 High

    Mapping the dynamic cell-cycle relocalization of PP1γ placed the phosphatase at successive mitotic structures, framing it as a regulator of segregation and cytokinesis.

    Evidence Live-cell time-lapse imaging and FRAP of FP-PP1γ in stable HeLa lines

    PMID:12529430

    Open questions at the time
    • Localization alone did not identify the targeting subunits driving each relocalization
    • No substrate dephosphorylated at each site identified
  4. 2007 High

    Identifying URI as an inhibitory mitochondrial partner released by S6K1 phosphorylation revealed how PP1γ activity is switched on to drive an apoptotic feedback loop, and a germline knockout established its essential role in spermiogenesis.

    Evidence Co-IP, in vitro phosphatase assays and URI-S371 mutagenesis (mitochondrial complex); Ppp1cc knockout mice with sperm ultrastructure EM

    PMID:17301292 PMID:17936702

    Open questions at the time
    • URI study did not resolve whether other regulatory subunits compete for the same pool
    • Knockout did not distinguish PP1γ1 vs PP1γ2 contributions in vivo
  5. 2011 High

    Resolving the Plk1–Mst2–Nek2A–PP1γ circuit showed PP1γ is recruited via Mst2 to oppose centrosome disjunction, with Plk1 acting as the switch that excludes it.

    Evidence Reciprocal Co-IP, kinase assays, Mst2 phosphomutants and centrosome separation assays

    PMID:21723128

    Open questions at the time
    • Direct Nek2A substrate dephosphorylated by PP1γ not defined
    • Quantitative contribution to disjunction timing unresolved
  6. 2009 High

    Isoform-specific transgenic rescue showed PP1γ2 alone restores spermatid viability but not flagellar morphogenesis, establishing non-redundant requirements for both isoforms in spermatogenesis.

    Evidence Transgenic PPP1CC2 rescue in Ppp1cc-null mice with morphology, motility and fertility readouts

    PMID:19420386

    Open questions at the time
    • Substrates underlying flagellar morphogenesis not identified
    • Mechanism of the anti-apoptotic effect on spermatids unresolved
  7. 2010 Medium

    Stage-specific phenotyping localized PP1γ function to acrosome development and chromatin compaction in elongating spermatids.

    Evidence Light and electron microscopy of Ppp1cc knockout seminiferous epithelium

    PMID:20385779

    Open questions at the time
    • No molecular substrate of chromatin condensation identified
    • Single-lab study
  8. 2012 High

    Linking PP1γ to the SMN complex through Gemin8 added a role in regulating SMN phosphorylation and subnuclear assembly.

    Evidence Reciprocal Co-IP, in vitro binding, RNAi and 2D phospho-gel analysis in HeLa cells

    PMID:22454514

    Open questions at the time
    • Direct SMN phospho-site dephosphorylated not mapped
    • Physiological consequence for snRNP biogenesis not assayed
  9. 2013 High

    Three independent studies expanded PP1γ's isoform-specific partnerships — hScrib for ERK suppression and tumor restraint, ASF for CaMKIIδ splicing, and confirmation that germ-cell PP1γ2 alone dictates fertility.

    Evidence MS/Co-IP and motif-mutant binding (hScrib); Co-IP and splicing reporters (ASF/CaMKIIδ); Stra8-Cre conditional Ppp1cc knockout (germ cells)

    PMID:23359326 PMID:24089200 PMID:24196533

    Open questions at the time
    • hScrib- and ASF-directed substrates not biochemically defined
    • Whether these signaling roles use PP1γ1 or PP1γ2 not fully resolved
  10. 2014 Medium

    PP1γ was shown to enhance TRAF6 E3 ligase activity and NF-κB innate immune signaling, an effect dependent on catalytic activity.

    Evidence Gain-of-function screen, Co-IP, ubiquitination assays with catalytically inactive PP1γ, immune activation assays

    PMID:24586659

    Open questions at the time
    • Phosphatase substrate controlling TRAF6 activity unidentified
    • Single-lab study
  11. 2016 Medium

    Defining the NEK1–PP1γ–WAPL axis showed PP1γ phosphorylation by NEK1 enables WAPL dephosphorylation to drive meiotic cohesin removal.

    Evidence Co-IP, phosphorylation assays and Nek1 knockout mouse meiotic chromosome analysis

    PMID:27760328

    Open questions at the time
    • WAPL phospho-sites targeted not mapped
    • Single-lab study
  12. 2018 Medium

    An α7nAChR–PP1γ interaction was shown to feed the TRAF6/NF-κB axis to promote hepatocellular carcinoma proliferation.

    Evidence Co-IP, siRNA, ubiquitination and NF-κB reporter assays in HCC cells

    PMID:30074282

    Open questions at the time
    • Direct PP1γ substrate in the pathway undefined
    • Single-lab cancer-cell study
  13. 2020 Medium

    Showing Aurora B phosphorylates Repo-Man to evict PP1γ from mitotic chromatin explained how the chromatin phosphorylation state is held high during mitosis.

    Evidence Co-IP, Repo-Man phosphomutants, Aurora B inhibition and ectopic PP1γ targeting constructs

    PMID:32938714

    Open questions at the time
    • Chromatin substrates kept phosphorylated not enumerated
    • Single-lab study
  14. 2021 High

    A genome-wide screen identified PPP1R3G as the targeting subunit that recruits PP1γ to dephosphorylate inhibitory RIPK1 phospho-sites and license apoptosis/necroptosis.

    Evidence CRISPR screen, Co-IP, RIPK1-S25 phospho-antibodies, binding-mutant rescue and Ppp1r3g knockout mice

    PMID:34862394

    Open questions at the time
    • Full set of RIPK1 sites dephosphorylated not exhaustively mapped
    • Crosstalk with URI-controlled apoptotic pool not addressed
  15. 2022 High

    Two studies placed PP1γ in neuronal regulation — within an HDAC1/PP1γ complex that dephosphorylates CREB-Ser133 in dopaminergic neurodegeneration, and in isoform-specific control of synaptic transmission via I-2 and neurabin.

    Evidence Co-IP, proximity ligation in PD tissue, MPTP mouse model (CREB); electrophysiology and FRET/FLIM with I-2 phosphomutants (synapse)

    PMID:35501151 PMID:36276179

    Open questions at the time
    • How HDAC1 complex assembly is regulated in disease unresolved
    • Synaptic substrate set of PP1γ not defined
  16. 2023 Medium

    PP1γ was shown to specifically regulate neuronal insulin signaling by dephosphorylating AKT2, tying PP1γ imbalance to an Alzheimer's-like phenotype.

    Evidence Isoform-specific siRNA, phospho-AKT2/AS160/GSK3 westerns, GLUT4 imaging and high-fat-diet mouse brain lysates

    PMID:37085815

    Open questions at the time
    • Direct AKT2 phospho-site dephosphorylated not mapped
    • Single-lab study
  17. 2024 Medium

    Identifying gp78-mediated ubiquitin degradation of PPP1CC as a control on KAP1 dephosphorylation linked PP1γ turnover to DNA damage repair and radioresistance.

    Evidence Co-IP, ubiquitination assays, phospho-KAP1 westerns and radiation survival assays in breast cancer cells

    PMID:39297166

    Open questions at the time
    • Whether KAP1 is a direct PP1γ substrate not demonstrated
    • Single-lab study
  18. 2025 Medium

    Multiple 2025 studies converged on PP1γ as a YAP/Hippo regulator — driving trophectoderm specification via GAS5-restricted localization, promoting ESCC progression through YAP1/SOX2, and integrating JNK-dependent apoptosis/ferroptosis.

    Evidence Embryo knockdown with phospho-YAP imaging and GAS5 manipulation; ESCC siRNA with p-YAP1/SOX2 readouts; Drosophila epistasis and human liver tumor cell assays

    PMID:40626009 PMID:40906558 PMID:41403070

    Open questions at the time
    • Direct YAP phospho-sites dephosphorylated by PP1γ not biochemically mapped
    • ESCC finding is Low-confidence with no direct phosphatase-substrate demonstration
  19. 2026 Low

    Proteomic profiling of the testis PP1γ2 interactome nominated novel partners (PIHI1D1, ZFR, NDUFB10, ILF2, TBLX1R1) implicating PP1γ2 in splicing and gene-expression machinery during sperm formation.

    Evidence Immunoprecipitation followed by LC-MS/MS from testis tissue

    PMID:41913519

    Open questions at the time
    • Single pulldown-MS with no functional validation of most interactions
    • Direct binding versus complex co-purification not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single catalytic subunit achieves substrate selectivity at each site — the complete map of regulatory/targeting subunit, isoform identity, and the specific phospho-sites dephosphorylated — remains the central open question.
  • Most reported substrates lack mapped dephosphorylation sites
  • Isoform (PP1γ1 vs PP1γ2) responsible for each non-testis role often unresolved
  • Quantitative competition between regulatory subunits for the catalytic pool uncharacterized

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 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005730 nucleolus 1 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1474165 Reproduction 4 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2
Partners
GEMIN8HDAC1HSCRIBMST2PPP1R3GREPO-MANURIWAPL
Complex memberships
HDAC1/PP1γ complexNek2A–PP1γ–Mst2 complexSMN complexURI/PP1γ mitochondrial complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 PP1γ dynamically relocalizes throughout the mammalian cell cycle: it accumulates in nucleoli during interphase, localizes to kinetochores in early mitosis (with rapid exchange with the cytoplasmic pool), redistributes to chromosome-containing regions at the early-to-late anaphase transition, and accumulates at the cleavage furrow and midbody by telophase, implicating it in nucleolar function, chromosome segregation, and cytokinesis. Stable HeLa cell lines expressing FP-PP1γ fusion proteins; time-lapse fluorescence imaging; FRAP Molecular biology of the cell High 12529430
2007 URI forms stable complexes with PP1γ at mitochondria in growth-factor-deprived or rapamycin-treated cells, inhibiting the bound PP1γ activity. S6K1-mediated phosphorylation of URI at serine 371 upon growth factor stimulation disassembles the URI/PP1γ complex, releasing active PP1γ that then dephosphorylates and reduces S6K1 activity and BAD phosphorylation, thus activating a negative feedback loop that lowers the threshold for apoptosis. Co-immunoprecipitation, in vitro phosphatase activity assays, phosphospecific antibodies, S6K1 kinase assays, rapamycin treatment, MS identification Molecular cell High 17936702
2011 Plk1 phosphorylates Mst2 to prevent assembly of Nek2A–PP1γ–Mst2 complexes. In the absence of Plk1 phosphorylation of Mst2, PP1γ is recruited into the complex via Mst2 and counteracts Nek2A kinase activity (opposing centrosome disjunction). Plk1-phosphorylated Mst2 cannot bind PP1γ, thus allowing Nek2A activity to proceed and drive centrosome disjunction. Co-immunoprecipitation, kinase assays, Plk1 inhibitor/depletion, Mst2 phosphorylation-site mutants, centrosome separation assays Current biology : CB High 21723128
1993 Alternative splicing of the PPP1CC gene produces two PP1γ isoforms (PP1γ1 and PP1γ2) that differ at their C-termini. The gene was mapped to human chromosome 12q24.1–q24.2, distinct from the PP1α locus on chromosome 11. cDNA cloning from human teratocarcinoma library; somatic cell hybrid DNA analysis; in situ hybridization (FISH) Biochimica et biophysica acta High 8394140
1997 Both PP1γ1 and PP1γ2 isoforms encoded by Ppp1cc retain phosphatase function, as demonstrated by their ability to complement the cold-sensitive PP1 defect (dis2-11 mutation) in fission yeast S. pombe. Complementation of fission yeast dis2-11 cold-sensitive mutant; Southern hybridization; FISH mapping Genomics Medium 9339378
2007 Targeted disruption of Ppp1cc in mice causes male infertility due to impaired spermiogenesis; PP1γ2 is the predominant isoform in spermatids and spermatozoa, and its loss produces malformed mitochondrial sheaths and extra outer dense fibers in sperm tails, implicating PP1γ2 in sperm tail morphogenesis in addition to motility. Ppp1cc knockout mice; isoform-specific immunohistochemistry; electron microscopy of sperm ultrastructure Biology of reproduction High 17301292
2009 Transgenic expression of PPP1CC2 alone in Ppp1cc-null testes rescues spermatid viability and spermiation (anti-apoptotic effect) but fails to restore normal flagellar morphogenesis, sperm motility, or fertility, indicating that both PPP1CC isoforms are required for structurally normal spermatogenesis. Transgenic rescue experiment in Ppp1cc-/- mice; sperm morphology and motility analysis; fertility testing Biology of reproduction High 19420386
2010 Loss of PP1γ in Ppp1cc knockout mice produces acrosomal defects and chromatin condensation defects in elongating spermatids, while junction complexes remain ultrastructurally normal, localizing PP1γ function to acrosome development and chromatin compaction during spermiogenesis. Light and electron microscopy of Ppp1cc knockout seminiferous epithelium; stage-specific analysis Reproduction (Cambridge, England) Medium 20385779
2012 PP1γ directly interacts with the SMN complex component Gemin8; PP1γ depletion by RNAi leads to hyperphosphorylation of SMN (revealed by 2D gel electrophoresis) and enhanced localization of the SMN complex and snRNPs to Cajal bodies, demonstrating that PP1γ dephosphorylates SMN to regulate SMN complex assembly and subnuclear localization. Co-immunoprecipitation from HeLa extracts, in vitro protein binding assays, RNAi knockdown, 2D gel electrophoresis, immunofluorescence Journal of cell science High 22454514
2013 PP1γ is a direct interacting partner of hScrib (via a conserved PP1γ interaction motif on hScrib); this interaction is required for hScrib-mediated downregulation of ERK phosphorylation and for hScrib's ability to suppress oncogene-induced transformation. Loss of hScrib enhances nuclear translocation of PP1γ. Proteomic/mass spectrometry identification, co-immunoprecipitation, in vitro binding assays, ERK phosphorylation assays, oncogenic transformation assays, immunofluorescence PloS one High 23359326
2013 PP1γ (but not PP1α or PP1β) specifically enhances alternative splicing of CaMKIIδ by interacting with the splicing factor ASF; PP1γ overexpression or inhibition respectively promotes or suppresses CaMKIIδ splicing and associated cardiomyocyte apoptosis in OGD/R conditions. Co-immunoprecipitation of ASF-PP1γ, splicing reporter assays, PP1γ overexpression/siRNA in HEK293T and primary cardiomyocytes, pharmacological PP1 inhibition American journal of physiology. Cell physiology Medium 24196533
2013 Germ-cell-specific deletion of Ppp1cc (using Stra8-Cre) phenocopies global knockout, confirming that PPP1CC2 function in meiotic and postmeiotic germ cells is the critical determinant of male fertility; PPP1CC2 is the only PP1 isoform absent from Sertoli cells and spermatogonia but present in postmeiotic germ cells. Conditional (Stra8-Cre) Ppp1cc knockout mice; isoform-specific immunostaining; fertility assessment; sperm analysis Biology of reproduction High 24089200
2014 PP1γ physically interacts with TRAF6 and enhances TRAF6 E3 ubiquitin ligase activity toward itself and substrates such as IKKγ, thereby promoting NF-κB-mediated innate immune signaling; enzymatically inactive PP1γ represses these events. Gain-of-function genetic screen, co-immunoprecipitation, ubiquitination assays with wild-type and catalytically inactive PP1γ, macrophage/monocyte innate immune activation assays PloS one Medium 24586659
2016 NEK1 phosphorylates PP1γ; phosphorylated PP1γ in turn dephosphorylates WAPL, retaining WAPL on chromosome cores to promote cohesin removal along chromosome arms during meiotic prophase I. This NEK1–PP1γ–WAPL axis operates through NEK1 interaction with PDS5B. Co-immunoprecipitation, phosphorylation assays, Nek1 knockout mice meiotic chromosome analysis, immunofluorescence of cohesin/WAPL localization Cell reports Medium 27760328
2018 α7 nicotinic acetylcholine receptor (α7nAChR) interacts with PP1γ in hepatocellular carcinoma cells; ligand-bound α7nAChR facilitates PP1γ-dependent ubiquitination and activation of TRAF6, leading to IκBα degradation, NF-κB nuclear accumulation, and upregulation of Cyclin D1 and PCNA. Co-immunoprecipitation, siRNA knockdown, ubiquitination assays, NF-κB reporter assays, proliferation assays Molecular carcinogenesis Medium 30074282
2020 Aurora B phosphorylates the PP1γ regulatory subunit Repo-Man to disrupt the PP1γ–Repo-Man interaction on chromatin, causing PP1γ dissociation from mitotic chromosomes; this dissociation is required to maintain the high chromatin phosphorylation state during mitosis. Repo-Man phosphorylation-site mutants or Aurora B inhibition retain PP1γ on chromatin and prolong chromosome condensation. Co-immunoprecipitation, immunofluorescence microscopy, Aurora B inhibitor treatment, Repo-Man phosphomutant overexpression, ectopic PP1γ targeting constructs The Journal of biological chemistry Medium 32938714
2021 PPP1R3G recruits PP1γ to RIPK1-containing complex I, where PP1γ removes inhibitory phosphorylations on RIPK1 (including serine 25), activating RIPK1 kinase activity and enabling apoptosis and necroptosis. A PPP1R3G mutant unable to bind PP1γ fails to rescue RIPK1 activation. Ppp1r3g-/- mice are protected from TNF-induced systemic inflammatory response syndrome. CRISPR whole-genome knockout screen, co-immunoprecipitation, phosphospecific antibodies for RIPK1-S25, PPP1R3G binding-mutant rescue, Ppp1r3g-/- mouse model Nature communications High 34862394
2022 PP1γ is constitutively associated with HDAC1; the HDAC1/PP1γ complex dephosphorylates CREB at Ser133 during dopaminergic neurodegeneration, inactivating CREB and reducing expression of its target NURR1. CREB interacts with the HDAC1/PP1γ complex in PD, and disrupting CREB/HDAC1 interaction restores phospho-CREB and NURR1 levels. Co-immunoprecipitation, proximity ligation assay (PD patient tissue), MPTP mouse model, phosphospecific CREB-S133 antibodies, HDAC inhibitor (trichostatin A) treatment, GAL4-M1 CREB mutant overexpression The Journal of neuroscience High 35501151
2022 PP1γ (but not PP1α) and inhibitor-2 (I-2) positively regulate synaptic transmission in hippocampal neurons; I-2 enhances PP1γ interaction with its synaptic scaffold neurabin (measured by FRET/FLIM), and I-2 threonine-72 phosphorylation dictates its in vivo effect on PP1 activity. Electrophysiology in hippocampal neurons, FRET/FLIM to measure PP1γ–neurabin interaction, I-2 phosphorylation-site mutants, isoform-specific knockdown Frontiers in synaptic neuroscience Medium 36276179
2023 PP1γ (but not PP1α) regulates neuronal insulin signaling by dephosphorylating AKT2, modulating the AKT2–AS160–GLUT4 axis and GLUT4 translocation; it also regulates GSK3β phosphorylation via AKT2, and GSK3α phosphorylation via MLK3, with imbalance producing an Alzheimer's disease-like phenotype. siRNA knockdown of PP1α and PP1γ in N2a and SH-SY5Y cells, western blot for phospho-AKT2/AS160/GSK3, confocal microscopy for GLUT4 translocation, fluorescence-based glucose uptake assay, high-fat-diet diabetic mouse model brain lysates Cell communication and signaling : CCS Medium 37085815
2024 gp78 E3 ubiquitin ligase degrades PPP1CC (and PPP2CA) via ubiquitination, thereby preventing dephosphorylation of KAP1 and promoting DNA damage repair and radioresistance in breast cancer cells. Co-immunoprecipitation, ubiquitination assays, western blot for phospho-KAP1, PPP1CC overexpression/knockdown, radiation survival assays iScience Medium 39297166
2025 PPP1CC (Drosophila ortholog Pp1-87B) dephosphorylates substrates to suppress JNK signaling via the Moe-Rho1 axis; impaired Pp1-87B/PPP1CC activates JNK, which integrates apoptosis and ferroptosis-like cell death through Hippo pathway activation. In human liver tumor cells, PPP1CC similarly drives apoptosis and ferroptosis via JNK activation. Drosophila genetic screen, epistasis analysis (double mutants), human liver cancer cell overexpression/knockdown, JNK pathway reporters, cell death assays Cell reports Medium 40906558
2025 PPP1CC dephosphorylates YAP in outer cells of the mouse morula, promoting YAP nuclear translocation and trophectoderm (TE) lineage specification. PPP1CC localization to the TE is spatially restricted by its interaction with the lncRNA GAS5, which localizes to the subcortical region throughout early embryogenesis. PPP1CC knockdown in preimplantation mouse embryos, immunofluorescence for phospho-YAP and YAP localization, GAS5 knockdown/overexpression, blastomere fate tracing Cell proliferation Medium 41403070
2025 PP1γ promotes ESCC progression by dephosphorylating YAP1, leading to reduced p-YAP1/YAP1 ratio, YAP1 activation, and upregulation of SOX2; silencing PPP1CC increases p-YAP1 and reduces SOX2, suppressing proliferation, migration, and invasion. PPP1CC siRNA knockdown in KYSE150 cells, western blot for p-YAP1/YAP1/SOX2, CCK-8 proliferation assay, colony formation, Transwell invasion/migration assays Frontiers in oncology Low 40626009
2026 PP1γ2 (testis-enriched isoform of PPP1CC) interacts with novel testicular partners including PIHI1D1 (part of the R2TP chaperone complex) and ZFR, NDUFB10, ILF2 (predicted via the C-terminal PP1γ2-specific sequence), as well as with SRPK1 interactome members ILF2 and TBLX1R1, suggesting additional roles in splicing, gene expression, and sperm formation. Immunoprecipitation followed by LC-MS/MS (testis tissue) Proteomics Low 41913519

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Time-lapse imaging reveals dynamic relocalization of PP1gamma throughout the mammalian cell cycle. Molecular biology of the cell 125 12529430
2011 Plk1 controls the Nek2A-PP1γ antagonism in centrosome disjunction. Current biology : CB 112 21723128
2007 S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Molecular cell 96 17936702
1993 Sequence of human protein serine/threonine phosphatase 1 gamma and localization of the gene (PPP1CC) encoding it to chromosome bands 12q24.1-q24.2. Biochimica et biophysica acta 64 8394140
2007 Analysis of Ppp1cc-null mice suggests a role for PP1gamma2 in sperm morphogenesis. Biology of reproduction 54 17301292
2013 Selective ablation of Ppp1cc gene in testicular germ cells causes oligo-teratozoospermia and infertility in mice. Biology of reproduction 37 24089200
2021 RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1γ promote apoptosis and necroptosis. Nature communications 33 34862394
2016 Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse. Cell reports 29 27760328
2021 Circular RNA PPP1CC promotes Porphyromonas gingivalis-lipopolysaccharide-induced pyroptosis of vascular smooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway. The Journal of international medical research 28 33769113
2013 A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation. PloS one 24 23359326
2022 CREB Inactivation by HDAC1/PP1γ Contributes to Dopaminergic Neurodegeneration in Parkinson's Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 35501151
2012 A protein phosphatase 1 gamma (PP1γ) of the human protozoan parasite Trichomonas vaginalis is involved in proliferation and cell attachment to the host cell. International journal for parasitology 23 22713760
2012 A role for protein phosphatase PP1γ in SMN complex formation and subnuclear localization to Cajal bodies. Journal of cell science 22 22454514
2014 The effect of hypoxia preconditioning on DNA methyltransferase and PP1γ in hippocampus of hypoxia preconditioned mice. High altitude medicine & biology 19 25531462
2010 Loss of protein phosphatase 1c{gamma} (PPP1CC) leads to impaired spermatogenesis associated with defects in chromatin condensation and acrosome development: an ultrastructural analysis. Reproduction (Cambridge, England) 19 20385779
1997 Genomic organization and functional analysis of the murine protein phosphatase 1c gamma (Ppp1cc) gene. Genomics 19 9339378
2018 α7nAChR-mediated recruitment of PP1γ promotes TRAF6/NF-κB cascade to facilitate the progression of Hepatocellular Carcinoma. Molecular carcinogenesis 18 30074282
2016 Effects of 5-Aza-2'-deoxycytidine on expression of PP1γ in learning and memory. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 27665473
2014 Positive regulation of TRAF6-dependent innate immune responses by protein phosphatase PP1-γ. PloS one 14 24586659
2013 PP1γ functionally augments the alternative splicing of CaMKIIδ through interaction with ASF. American journal of physiology. Cell physiology 14 24196533
2009 Expression of transgenic PPP1CC2 in the testis of Ppp1cc-null mice rescues spermatid viability and spermiation but does not restore normal sperm tail ultrastructure, sperm motility, or fertility. Biology of reproduction 13 19420386
2011 Identification and prioritization of NUAK1 and PPP1CC as positional candidate loci for skeletal muscle strength phenotypes. Physiological genomics 11 21750233
2017 PPP1CC is associated with astrocyte and microglia proliferation after traumatic spinal cord injury in rats. Pathology, research and practice 10 29033188
2015 Micro(mi) RNA-34a targets protein phosphatase (PP)1γ to regulate DNA damage tolerance. Cell cycle (Georgetown, Tex.) 7 26111201
2021 miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells. Diabetes, metabolic syndrome and obesity : targets and therapy 6 34113143
2020 Aurora B regulates PP1γ-Repo-Man interactions to maintain the chromosome condensation state. The Journal of biological chemistry 6 32938714
2023 PP1γ regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes. Cell communication and signaling : CCS 5 37085815
2024 gp78-regulated KAP1 phosphorylation induces radioresistance in breast cancer by facilitating PPP1CC/PPP2CA ubiquitination. iScience 4 39297166
2022 Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission. Frontiers in synaptic neuroscience 4 36276179
2024 Target silencing of porcine SPAG6 and PPP1CC by shRNA attenuated sperm motility. Theriogenology 3 38430798
2024 CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1γ-Dependent Inhibition of AKT Signaling. Pharmaceutics 3 39339236
2013 PP-1α and PP-1γ display antagonism and differential roles in tumorigenicity of lung cancer cells. Current molecular medicine 3 23176181
1996 Assignment of the gene encoding type 1 gamma protein phosphatase catalytic subunit (PPP1CC) on human, rat, and mouse chromosomes. The Japanese journal of human genetics 2 8914631
2025 PP1γ promotes esophageal squamous cell carcinoma progression through the PP1γ/YAP1/SOX2 axis. Frontiers in oncology 1 40626009
2025 Pp1-87B/PPP1CC-JNK axis integrates apoptosis and ferroptosis-like cell death to regulate cell competition and tumorigenesis. Cell reports 1 40906558
2025 Phosphatase PPP1CC Regulates the First Lineage Segregation by GAS5 in Mouse Preimplantation Embryos. Cell proliferation 1 41403070
2016 STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1γ in Lymphoblastic Leukemia. Current molecular medicine 1 27758712
2026 Multiple Roles of Protamine Kinase SRPK1 and Phosphatase PP1γ in Sperm Development. Proteomics 0 41913519
2026 Asiaticoside Alleviates Alzheimer's Disease by Regulating PPP1CC Expression to Suppress Inflammation and Mitochondrial Dysfunction. Annals of clinical and laboratory science 0 41927108
2026 PPP1CC Suppresses Preadipocyte Differentiation in Chickens at Least Partly by Regulating NRF1 Expression. Genes 0 42074493

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