Affinage

PCK1

Phosphoenolpyruvate carboxykinase, cytosolic [GTP] · UniProt P35558

Length
622 aa
Mass
69.2 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCK1 (PEPCK-C) is a cytosolic enzyme whose canonical conversion between oxaloacetate and phosphoenolpyruvate places it at the control point of gluconeogenesis, glyceroneogenesis, and TCA cataplerosis, but which moonlights as a signaling kinase and metabolic node that shapes cancer, metabolic, and immune phenotypes (PMID:23466304, PMID:29335519, PMID:20124556). Liver PCK1 is the critical determinant of systemic glucose homeostasis, as neonatal liver-specific re-expression rescues the lethal hypoglycemia of whole-body knockouts, while the mitochondrial isoform PEPCK-M can partially substitute for its gluconeogenic and TCA functions (PMID:27785616, PMID:23466304). In adipose tissue PPARgamma-driven PCK1 sustains glyceroneogenesis required for normal lipid and glucose homeostasis, and in kidney proximal tubule PCK1 supports ammoniagenesis, ATP production, and mitoribosomal integrity against acidosis and diabetic fibrosis (PMID:20124556, PMID:37102687, PMID:37199399). Beyond catalysis, AKT phosphorylation at Ser90 relocates PCK1 to the ER where it functions as a GTP-dependent protein kinase that phosphorylates INSIG1/INSIG2, releasing SCAP-SREBP to drive lipogenesis—an axis co-opted in HCC and by viral infection (PMID:32322062, PMID:39433189). PCK1 activity is gated by acetylation: active-site self-acetylation at K244 using acetyl-CoA inhibits the enzyme, while K91 acetylation reverses its directional preference toward anaplerotic OAA synthesis to suppress gluconeogenesis (PMID:33334880, PMID:39341205). As a tumor suppressor in liver, PCK1 loss elevates oxaloacetate and GTP to drive global O-GlcNAcylation of CHK2 and KAT5 promoting proliferation and metastasis, reduces SAM-dependent H3K9me3 to de-repress S100A11/AKT signaling, and activates GTP-dependent RhoA/PI3K/AKT and PDGF-AA signaling that promotes hepatic fibrosis (PMID:33690219, PMID:34650217, PMID:37166978, PMID:36918564). PCK1 also competitively consumes GTP to suppress cGAS-STING upon JNK-mediated Ser151 phosphorylation, enabling tumor immune evasion (PMID:40048154), and supports redox homeostasis by feeding glycogen-derived flux into the pentose phosphate pathway for NADPH generation in memory CD8+ T cells and chemoresistant cancer stem cells (PMID:29230018, PMID:38871968). Its expression is controlled by an interlocking transcriptional network including FOXO1-EHMT2, SHP-1/STAT5, REV-ERBalpha, RAR, ChREBP, and m6A mRNA modification (PMID:25736587, PMID:37595871, PMID:30639375, PMID:21519922, PMID:36455788, PMID:38085830).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2004 Medium

    Identifying the cis-element where the -232C/G promoter variant lies established a discrete DNA module mediating insulin-dependent repression of PCK1 transcription, explaining how hormonal signals tune gluconeogenic gene output.

    Evidence Luciferase reporter assays across three cell lines with promoter variant constructs

    PMID:14764811

    Open questions at the time
    • Does not identify the transcription factor binding the element
    • Population-level metabolic consequences not directly shown
  2. 2010 High

    Deleting the adipose PPARE answered whether adipose PCK1 contributes to whole-body metabolism, showing it is required for glyceroneogenesis and glucose homeostasis independent of liver gluconeogenesis.

    Evidence PPARE(-/-) mice with hyperinsulinemic-euglycemic clamp and islet secretion assays

    PMID:20124556

    Open questions at the time
    • Tissue-autonomous versus systemic contributions not fully separated
    • Molecular link between glyceroneogenesis and insulin resistance not detailed
  3. 2013 High

    Re-expressing each PEPCK isoform in liver-specific knockout mice resolved the relative gluconeogenic capacity of cytosolic versus mitochondrial PEPCK, showing PEPCK-M has independent gluconeogenic potential and cooperates with PCK1 in flux control.

    Evidence NMR (2H/13C) tracer studies in isolated KO livers with adenoviral isoform expression

    PMID:23466304

    Open questions at the time
    • Quantitative in vivo contribution of PEPCK-M in intact animals unresolved
    • Regulation distinguishing the two isoforms not addressed
  4. 2015 Medium

    Linking insulin-driven FOXO1 Ser256 phosphorylation to FOXO1-EHMT2 complex formation at the PCK1 promoter explained the chromatin mechanism by which insulin represses PCK1 transcription.

    Evidence Live-cell imaging, Co-IP, ChIP of promoter histone marks in cell models

    PMID:25736587

    Open questions at the time
    • NUP98 role mechanistically incomplete
    • In vivo relevance to hepatic gluconeogenesis not tested
  5. 2016 Medium

    A natural pig Met139Leu variant demonstrated that single residue changes shift PCK1 between glyceroneogenic and anaplerotic directions and alter its acetylation/degradation, connecting catalytic directionality to protein stability.

    Evidence In vitro kinetics of recombinant variant proteins plus cell culture glucose/lipid and acetylation assays

    PMID:26792594

    Open questions at the time
    • Human relevance of the variant not established
    • Structural basis of directional shift not resolved
  6. 2016 Medium

    Neonatal liver-specific re-expression in whole-body KO pups established that hepatic PCK1 is the critical determinant of survival-limiting hypoglycemia, isolating the liver's role from other tissues.

    Evidence Adenoviral liver re-expression in KO pups with glucose and survival readouts

    PMID:27785616

    Open questions at the time
    • Partial rescue only; non-hepatic contributions to phenotype remain
    • Long-term metabolic outcomes not assessed
  7. 2016 Medium

    Showing HBXIP suppresses PCK1 via miR-135a and PI3K/Akt-driven FOXO1 export, and that PCK1 overexpression abolishes HBXIP-driven growth, positioned PCK1 as a tumor suppressor downstream of an oncoprotein.

    Evidence 3'UTR luciferase, nuclear fractionation, PCK1 rescue in xenografts

    PMID:27609066

    Open questions at the time
    • Direct enzymatic mechanism of growth suppression not defined here
    • Relative weight of the two repression arms unquantified
  8. 2017 High

    Discovering that memory CD8+ T cells route PCK1-driven gluconeogenesis into glycogen and the PPP redefined PCK1 as a redox-supporting enzyme controlling immune memory rather than purely a glucose-producing one.

    Evidence Pck1 KO/KD in T cells with flux analysis, GSH/GSSG, ROS, and adoptive transfer

    PMID:29230018

    Open questions at the time
    • Upstream signals inducing PCK1 in T cells unclear
    • Generalizability to other immune subsets untested
  9. 2018 High

    Forced PCK1 expression in glucose-starved liver cancer cells driving catalysis-dependent TCA cataplerosis and apoptosis demonstrated that PCK1's enzymatic flux itself can be cytotoxic, providing a tumor-suppressive mechanism.

    Evidence Catalytic mutants, alpha-KG and ROS rescue, xenograft models

    PMID:29335519

    Open questions at the time
    • Context dependence on nutrient state not generalized
    • Does not address chronic low-level expression effects
  10. 2018 High

    Myeloid Pck1 deletion shifting macrophages toward M1 inflammatory phenotype with altered TCA labeling established a role for PCK1 in immunometabolic polarization.

    Evidence Myeloid-specific KO mouse with [U-13C]glucose flux tracing and cytokine assays

    PMID:29317502

    Open questions at the time
    • Molecular link between flux change and cytokine induction not defined
    • In vivo disease relevance not addressed
  11. 2019 Medium

    Demonstrating PCK1 overexpression triggers AMPK/p27Kip1-mediated G1 arrest, reversible by AMPK knockdown, provided an energy-sensing mechanism for PCK1's anti-proliferative effect in hepatoma.

    Evidence Gain/loss-of-function, flow cytometry, AMPK knockdown epistasis, xenografts

    PMID:30717766

    Open questions at the time
    • Whether ATP depletion is catalysis-dependent not fully shown
    • Relationship to cataplerosis-driven apoptosis unclear
  12. 2019 Medium

    Finding PCK1 drives hypoxic pyrimidine biosynthesis to enable colorectal liver metastasis revealed an oncogenic, gluconeogenesis-independent function opposite to its hepatic tumor-suppressor role.

    Evidence PDX metastatic selection, pyrimidine metabolomics, DHODH inhibition

    PMID:31841108

    Open questions at the time
    • Direct enzymatic link to pyrimidine pool not mechanistically resolved
    • Why context determines oncogenic vs suppressive role unexplained
  13. 2019 Medium

    Mapping REV-ERBalpha binding to a RevRE in the PCK1 promoter placed gluconeogenesis under direct circadian transcriptional control.

    Evidence Luciferase, EMSA, ChIP, SR9009 activation in diabetic mice

    PMID:30639375

    Open questions at the time
    • Integration with other promoter regulators not addressed
    • Diurnal dynamics in vivo not fully characterized
  14. 2020 High

    Discovering that AKT-phosphorylated PCK1 translocates to the ER and acts as a GTP-dependent protein kinase on INSIG1/2 to activate SREBP fundamentally reclassified PCK1 as a moonlighting kinase coupling metabolism to lipogenic gene transcription.

    Evidence Co-IP, in vitro kinase reconstitution, mutagenesis, fractionation, MS, xenografts

    PMID:32322062

    Open questions at the time
    • Structural basis of the kinase activity not defined
    • Balance between cytosolic enzyme and ER kinase pools unquantified
  15. 2021 High

    Structural and biophysical analysis showed active-site self-acetylation at K244 using acetyl-CoA inhibits PCK1 catalysis independently of p300, establishing a metabolite-driven autoregulatory switch.

    Evidence Crystallography, ITC, STD-NMR, docking, kinetics, mutagenesis

    PMID:33334880

    Open questions at the time
    • In vivo prevalence of self-acetylation not quantified
    • Deacetylase counteracting K244 not identified here
  16. 2021 High

    Linking PCK1 loss to oxaloacetate-driven O-GlcNAcylation of CHK2 explained how PCK1 deficiency destabilizes CHK2 and promotes HCC proliferation through hexosamine pathway flux.

    Evidence KO cells, flux analysis, O-GlcNAc IP/MS, liver KO mice, HBP inhibition

    PMID:33690219

    Open questions at the time
    • Site-specific reversibility of CHK2 O-GlcNAcylation in vivo not detailed
    • Contribution of AMPK-GFAT1 versus UDP-GlcNAc arm not separated
  17. 2021 High

    Showing PCK1 depletion stabilizes O-GlcNAcylated KAT5 to drive EMT-promoting transcription extended the O-GlcNAcylation mechanism to metastasis.

    Evidence Gain/loss-of-function, Co-IP, ubiquitination, ChIP, Pck1-deletion mice, metastasis assays

    PMID:34650217

    Open questions at the time
    • Whether CHK2 and KAT5 effects are independent or coupled unclear
    • Therapeutic targeting of the O-GlcNAc node not tested
  18. 2023 High

    Connecting PCK1 to SAM-dependent H3K9me3 at the S100A11 promoter revealed an epigenetic mechanism by which PCK1 loss de-represses an AKT-activating oncogene.

    Evidence Metabolomics, Co-IP, ChIP, SAM rescue, S100A11 KO in vivo

    PMID:37166978

    Open questions at the time
    • Direct flux from PCK1 to SAM not fully traced
    • Generality across other H3K9me3 loci unknown
  19. 2023 High

    Showing PCK1 deficiency raises intracellular GTP to activate RhoA/PI3K/AKT and PDGF-AA secretion driving stellate cell activation defined a mechanism for PCK1 loss in MAFLD fibrosis.

    Evidence Liver-specific KO mice, AAV rescue, RhoA/AKT inhibition and silencing, GTP and PDGF-AA measurements

    PMID:36918564

    Open questions at the time
    • How GTP accumulation specifically activates RhoA not detailed
    • Reversibility of established fibrosis not tested
  20. 2023 Medium

    Identifying SHP-1/STAT5 recruitment of RNA polymerase II to the PCK1 promoter added a transcriptional coactivation route controlling gluconeogenic output.

    Evidence Co-IP, ChIP-seq, loss-of-function with gluconeogenesis readout

    PMID:37595871

    Open questions at the time
    • Phosphatase activity versus scaffold role of SHP-1 not separated
    • Physiological trigger for this axis unclear
  21. 2023 Medium

    m6A-reader and writer studies (hnRNPA2B1 destabilizing, METTL3 stabilizing PCK1 mRNA) established post-transcriptional m6A control of PCK1 levels in HCC and ischemia-reperfusion injury.

    Evidence RIP, MeRIP, m6A-seq, CRISPR KO, conditional METTL3 KO, in vivo models

    PMID:38017546 PMID:38085830

    Open questions at the time
    • Reconciliation of opposing m6A effects on stability versus export incomplete
    • Site-specific m6A residues on PCK1 transcript not mapped
  22. 2023 High

    Kidney- and proximal-tubule-specific KO/transgenic models established PCK1 as essential for renal ammoniagenesis, acid-base balance, ATP supply, and mitoribosomal integrity against diabetic injury.

    Evidence Conditional KO and knockin/transgenic mice, metabolic and fibrosis phenotyping

    PMID:37102687 PMID:37199399

    Open questions at the time
    • Mechanism linking PCK1 to mitoribosome maintenance unresolved
    • Whether HK2 suppression is direct or metabolic not defined
  23. 2024 High

    Demonstrating that K91 acetylation reverses PCK1's directional preference toward anaplerotic OAA synthesis and that the K91Q mimetic ameliorates hyperglycemia established acetylation as a directional switch with therapeutic relevance.

    Evidence K91Q mimetic, flux analysis, hepatocyte assays, liver K91Q expression in obese mice, Seahorse

    PMID:39341205

    Open questions at the time
    • Endogenous regulation of K91 acetylation stoichiometry unclear
    • Long-term consequences of directional reversal untested
  24. 2024 Medium

    Showing PCK1 phosphorylates PYGL to enhance glycogenolysis and PPP-derived NADPH in cervical cancer stem cells extended the redox-support role to chemoresistance.

    Evidence siRNA knockdown, glycogen and PPP LC-MS, NADPH ratio, NSG tumor assays

    PMID:38871968

    Open questions at the time
    • Whether PCK1 directly phosphorylates PYGL not biochemically reconstituted
    • Relationship to ER kinase activity unclear
  25. 2024 Medium

    Several studies extended PCK1 regulation and function across tissues: RAR-mediated induction in hepatocytes, ChREBP/THR-coupled control driving beta-cell proliferation, UBAP2L dephosphorylation-driven autophagy suppressing CRC, intestinal epithelial effects in pancreatitis, and SIRT2-dependent stabilization in chondrocytes.

    Evidence Reporter/PLA/ChIP, Cre-Lox models, phospho-site analysis, pharmacological inhibition, and cell models

    PMID:21519922 PMID:36455788 PMID:37062825 PMID:38651689 PMID:39463224

    Open questions at the time
    • Several of these mechanisms rest on single-lab cell models
    • Direct enzymatic versus signaling contributions often not separated
  26. 2025 High

    Discovering that JNK-driven Ser151 phosphorylation lets PCK1 bind cGAS and competitively consume shared GTP to suppress cGAS-STING signaling defined a metabolite-competition mechanism for tumor immune evasion.

    Evidence Co-IP, GTP competition assays, site mutagenesis, STING reporters, tumor models with anti-PD-1, human specimens

    PMID:40048154

    Open questions at the time
    • Whether catalytic activity is required for GTP sequestration not fully separated
    • Relationship of Ser151 to other phospho-sites (Ser90) unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple post-translational switches (Ser90/Ser151 phosphorylation, K91/K244 acetylation, SIRT2 stabilization) are integrated to partition PCK1 between cytosolic gluconeogenic enzyme, ER/cGAS-bound GTP-consuming protein, and directional anaplerotic states in a given cell remains unresolved.
  • No unified structural or quantitative model of how modifications compete or cooperate
  • Tissue- and context-specific determinants of oncogenic versus tumor-suppressor behavior undefined
  • Stoichiometry of the moonlighting kinase pool versus catalytic pool in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3
Partners
CGASCHK2INSIG1INSIG2KAT5PYGLSIRT2UBAP2L

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 AKT phosphorylates PCK1 at Ser90 in hepatocellular carcinoma cells, causing PCK1 to translocate from the cytosol to the endoplasmic reticulum. At the ER, phosphorylated PCK1 acts as a protein kinase using GTP (not ATP) as phosphate donor to phosphorylate INSIG1 at Ser207 and INSIG2 at Ser151. This phosphorylation reduces sterol binding to INSIG1/2, disrupts INSIG-SCAP interaction, and allows SCAP-SREBP to translocate to the Golgi for SREBP activation and downstream lipogenesis gene transcription. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, subcellular fractionation, mass spectrometry, xenograft mouse models Nature High 32322062
2021 Self-acetylation of PCK1 at the active site using acetyl-CoA as substrate (independently of p300) inhibits enzymatic activity, producing a ~3-fold decrease in kcat without changes in Km. Acetylation of K244 inside the active site renders the enzyme inactive. Acetyl-CoA binding to the active site is specific and metal-dependent. Protein crystallization, mass spectrometry, isothermal titration calorimetry, saturation-transfer difference NMR, molecular docking, site-directed mutagenesis, in vitro kinetic assays The Journal of biological chemistry High 33334880
2021 PCK1 deficiency causes oxaloacetate accumulation, which increases de novo UTP synthesis contributing to UDP-GlcNAc biosynthesis, and also inactivates the AMPK-GFAT1 axis, together promoting global O-GlcNAcylation. Elevated O-GlcNAcylation results in CHK2 threonine 378 O-GlcNAcylation, which counteracts CHK2 stability and dimer formation, increases CHK2-dependent Rb phosphorylation, and promotes HCC cell proliferation. PCK1 knockout cells, metabolic flux analysis, Co-immunoprecipitation, O-GlcNAc immunoprecipitation, mass spectrometry, mouse liver-specific Pck1 knockout models, pharmacological inhibition of HBP The Journal of clinical investigation High 33690219
2021 PCK1 depletion increases O-GlcNAcylation of lysine acetyltransferase KAT5 (TIP60), suppressing KAT5 ubiquitination and thereby stabilizing KAT5. Stabilized O-GlcNAcylated KAT5 epigenetically activates TWIST1 expression via histone H4 acetylation and enhances MMP9 and MMP14 expression via c-Myc acetylation, promoting epithelial-mesenchymal transition and HCC metastasis. Gain- and loss-of-function experiments, Co-immunoprecipitation, ubiquitination assay, chromatin immunoprecipitation, hepatospecific Pck1-deletion mouse models, lung metastasis assays Oncogene High 34650217
2023 PCK1 fuels S-adenosylmethionine (SAM) generation through the serine synthesis pathway. SAM serves as methyl donor for SUV39H1-catalyzed H3K9me3 modification on the S100A11 oncogene promoter, suppressing S100A11 expression. PCK1 deficiency reduces SAM/H3K9me3, de-represses S100A11, which then interacts with AKT1 to upregulate PI3K/AKT signaling and promote HCC progression. Metabolomics, Co-immunoprecipitation, chromatin immunoprecipitation, SAM supplementation rescue experiments, S100A11 knockout in vivo, gain- and loss-of-function studies The Journal of clinical investigation High 37166978
2019 PCK1 negatively regulates hepatoma cell cycle progression via the AMPK/p27Kip1 axis: PCK1 overexpression reduces cellular ATP, enhances AMPK phosphorylation and p27Kip1 expression, and decreases Rb phosphorylation, causing G1 cell cycle arrest. AMPK knockdown reverses the G1 arrest caused by PCK1 overexpression. Gain- and loss-of-function experiments, flow cytometry, MTS assay, western blotting, AMPK knockdown epistasis, xenograft mouse models Journal of experimental & clinical cancer research Medium 30717766
2018 Forced PCK1 expression in glucose-starved liver cancer cells induces TCA cataplerosis, leading to energy crisis and oxidative stress that causes apoptosis. This pro-apoptotic effect requires PCK1 catalytic activity, as catalytic mutants fail to induce apoptosis. Replenishing TCA intermediate α-ketoglutarate or inhibiting ROS production blocks the cell death caused by PCK1 expression. Catalytic mutant expression, metabolite supplementation rescue, ROS inhibition rescue, cell death assays, xenograft mouse models Oncogene High 29335519
2017 CD8+ memory T cells upregulate PCK1 to drive gluconeogenesis, producing glycogen. This glycogen is channeled through glycogenolysis to generate glucose-6-phosphate and fuel the pentose phosphate pathway, generating NADPH and maintaining high reduced glutathione levels. Abrogation of the Pck1-glycogen-PPP axis decreases GSH/GSSG ratios, increases ROS, and impairs CD8+ memory T cell formation and maintenance. Pck1 knockout/knockdown in T cells, metabolic flux analysis, GSH/GSSG measurement, ROS measurement, adoptive transfer experiments, mouse tumor models Nature cell biology High 29230018
2019 PCK1 upregulation in colorectal cancer drives pyrimidine nucleotide biosynthesis under hypoxia, promoting liver metastatic colonization and growth. This function is distinct from its canonical gluconeogenic role and is suppressed by DHODH inhibitor leflunomide. In vivo PDX selection for metastatic colonization, metabolomics (pyrimidine intermediates), pharmacological inhibition, xenograft models eLife Medium 31841108
2023 PCK1 deficiency in the liver activates the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increases secretion of PDGF-AA, and promotes hepatic stellate cell activation to drive fibrosis. RhoA and AKT inhibition or gene silencing alleviated MAFLD in vivo. Liver-specific Pck1 knockout mice, adeno-associated virus PCK1 rescue, RhoA/AKT inhibitors and gene silencing, GTP measurement, PDGF-AA ELISA, in vivo models Nature communications High 36918564
2023 SHP-1 phosphatase acts as a transcriptional coactivator of PCK1 by being recruited to the PCK1 promoter regulatory regions via interaction with STAT5 and RNA polymerase II. Loss of SHP-1 or STAT5 decreases RNA polymerase II recruitment to the PCK1 promoter, reducing PCK1 mRNA levels and gluconeogenesis. Co-immunoprecipitation, chromatin immunoprecipitation sequencing (ChIP-seq), gluconeogenesis assays, SHP-1 and STAT5 loss-of-function The Journal of biological chemistry Medium 37595871
2025 Hypoxic stimulation induces JNK1/2-mediated S151 phosphorylation of PCK1, triggering interaction between PCK1 and cGAS. PCK1 associated with cGAS competitively consumes GTP (a shared substrate), inhibiting GTP-dependent cGAS activation and subsequent STING-mediated immune cell infiltration, thereby promoting tumor immune evasion. Co-immunoprecipitation, GTP competition assays, phosphorylation site mutagenesis, STING pathway reporters, mouse tumor models, combination with anti-PD-1 therapy, human breast cancer specimens The Journal of experimental medicine High 40048154
2024 SR18292 increases PCK1 acetylation at K91, which reverses the gluconeogenic reaction direction of PCK1 to favor OAA synthesis from phosphoenolpyruvate (anaplerotic direction). This PCK1 reverse catalytic reaction supplies OAA to the TCA cycle, increases glucose and lactate oxidation, and suppresses gluconeogenesis. Acetylation-mimetic PCK1 K91Q mutant expressed in mouse liver ameliorates hyperglycemia. Acetylation mimetic mutant (K91Q), metabolic flux analysis, hepatocyte gluconeogenesis assays, liver-specific K91Q Cre-Lox expression in obese mice, Seahorse metabolic analysis Cell chemical biology High 39341205
2016 A single amino acid substitution Met139Leu in pig PCK1 reduces kcat in the glyceroneogenic direction and enhances kcat in the anaplerotic direction, resulting in ~30% lower glucose and ~9% lower lipid production in cell cultures. The p.139L isoform also has compromised ability to be acetylated, increasing its susceptibility to ubiquitin-proteasome degradation. In vitro kinase/enzyme assays with purified recombinant proteins, cell culture glucose/lipid measurements, acetylation assays Scientific reports Medium 26792594
2015 Insulin-induced phosphorylation of FOXO1 at Ser256 (by Akt) causes translocation of FOXO1 from nuclear speckles to the nuclear periphery. This translocation is associated with formation of a FOXO1-EHMT2 complex and histone modifications at the PCK1 promoter region, leading to transcriptional repression of PCK1. FOXO1 uses nucleoporin NUP98 in this regulation. Live-cell imaging of FOXO1 localization, Co-immunoprecipitation (FOXO1-EHMT2), chromatin immunoprecipitation of PCK1 promoter histone marks, site-directed mutants, luciferase reporter assays Genes to cells Medium 25736587
2023 hnRNPA2B1 (an m6A reader) binds PCK1 mRNA and reduces its m6A methylation, leading to decreased PCK1 mRNA stability and expression. PCK1 knockout partially counteracted tumor inhibition by hnRNPA2B1 knockout, placing PCK1 downstream of hnRNPA2B1-mediated m6A regulation. RNA binding protein immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), CRISPR-Cas9 KO, RNA-seq, in vivo HCC mouse models Journal of translational medicine Medium 38017546
2023 Methyltransferase 3 (METTL3)-mediated N6-methyladenosine (m6A) modification of PCK1 mRNA transcript contributes to PCK1 upregulation during hepatic ischemia-reperfusion injury by increasing PCK1 mRNA export and expression. Hepatic-specific knockout of METTL3 reduces m6A deposition on PCK1 transcript and decreases PCK1 expression, worsening hepatic I/R injury. Human liver specimens, mouse I/R models, hepatocyte hypoxia/reoxygenation, METTL3 conditional KO, m6A sequencing, PCK1 overexpression rescue Hepatology Medium 38085830
2024 In cervical cancer stem cells, PCK1 enhances phosphorylation of PYGL (glycogen phosphorylase), increasing glycogen breakdown and shifting glucose metabolism towards the pentose phosphate pathway, generating NADPH. This facilitates ROS clearance and contributes to chemoresistance. siRNA knockdown of PCK1/PYGL/GYS1, glycogen measurement, PPP intermediate quantification by LC-MS, NADPH/NADP+ ratio, NSG mouse tumor growth assays Scientific reports Medium 38871968
2019 REV-ERBα (NR1D1) directly binds to a RevRE site at -325 to -320 bp in the PCK1 promoter to transcriptionally repress PCK1 expression, reducing hepatic gluconeogenesis and lowering plasma glucose in mice. Luciferase reporter assay, electromobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), SR9009 pharmacological activation, streptozotocin diabetic mouse model Pharmacological research Medium 30639375
2016 HBXIP oncoprotein inhibits PCK1 expression by downregulating transcription factor FOXO1 through two mechanisms: upregulating miR-135a targeting the 3'UTR of FOXO1 mRNA, and activating PI3K/Akt to phosphorylate FOXO1 and export it from the nucleus. Overexpression of PCK1 abolished HBXIP-promoted hepatoma cell growth in vitro and in vivo. miRNA target assays (3'UTR luciferase), western blotting of p-FOXO1, nuclear fractionation, PCK1 overexpression rescue, xenograft models Cancer letters Medium 27609066
2023 Kidney-specific PCK1 knockout in mice leads to hyperchloremic metabolic acidosis with reduced ammoniagenesis, glycosuria, lactaturia, altered systemic glucose and lactate metabolism, decreased ATP generation in proximal tubule cells, and increased tubular injury during metabolic acidosis. PCK1 overexpression in proteinuric chronic kidney disease preserves renal function. Kidney-specific KO and knockin mice (PAX8 promoter), acid-base and metabolic phenotyping, creatinine clearance, metabolomics, ATP measurements American journal of physiology. Renal physiology High 37102687
2023 In proximal tubule-specific Pck1 transgenic mice, PCK1 overexpression preserves mitoribosomal function and suppresses renal fibrosis in diabetic nephropathy. PCK1 overexpression also blocks upregulation of HK2 (the rate-limiting glycolysis enzyme), suppressing excess glycolysis. Proximal tubule-specific Pck1 CKO mice exhibit mitoribosomal defects and tubular apoptosis similar to diabetic mice. Proximal tubule-specific transgenic and conditional KO mice, STZ-induced diabetic model, mitoribosome integrity assays, fibrosis markers (collagen IV), albuminuria measurements Journal of the American Society of Nephrology High 37199399
2018 Myeloid cell-specific Pck1 deletion increases the proinflammatory M1 phenotype in macrophages. In LPS-stimulated bone marrow-derived macrophages, Pck1 deletion reduces 13C labeling of citrate and malate, increases 13C labeling of lactate, increases ROS, and elevates M1 cytokines TNFα, IL-1β, and IL-6. Myeloid-specific Pck1 knockout mouse, stable isotopomer MS analysis with [U-13C]glucose, cytokine ELISA, ROS measurement The Journal of biological chemistry High 29317502
2024 Retinoids induce PCK1 expression through retinoic acid receptor (RAR) activation via the proximal (not distal) RA-responsive element in the PCK1 promoter, and attenuate insulin-mediated suppression of PCK1 expression in primary rat hepatocytes. An RARα antagonist abolished retinal-mediated induction of PCK1. Promoter reporter assays, RAR/RXR selective agonists/antagonists, primary hepatocyte cultures, real-time PCR Molecular and cellular biochemistry Medium 21519922
2023 PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454, which enhances autophagy. PCK1 overexpression or knockdown experiments in CRC cells in vitro and in vivo showed that PCK1 inhibits CRC growth through this mechanism. PCK1 overexpression and knockdown in CRC cells, phosphorylation site analysis, autophagy assays, xenograft mouse models, immunohistochemistry Cancer cell international Medium 37062825
2013 In a liver-specific PEPCK-C (PCK1) knockout mouse, expressing the mitochondrial isoform PEPCK-M partially rescued defects in lipid metabolism, gluconeogenesis, and TCA cycle function, whereas ~10% re-expression of PEPCK-C normalized most parameters. This demonstrates that PEPCK-M has independent gluconeogenic potential and cooperates with PEPCK-C in adjusting gluconeogenic/TCA flux. NMR tracer studies (2H and 13C) in isolated livers, liver-specific KO mice, adenoviral PEPCK-M expression, primary hepatocyte metabolic profiling Journal of hepatology High 23466304
2024 PCK1 inhibition by 3-MPA in intestinal epithelial cells (IECs) alleviates acute pancreatitis by improving intestinal permeability, reducing epithelial apoptosis, increasing tight junction protein expression, restoring Paneth cell lysozyme and goblet cell MUC2 secretion, and improving intestinal immune response (elevated M2/M1 macrophage ratio, elevated sIgA). L-arginine-induced AP mouse model, Pck1 inhibitor 3-MPA, intestinal permeability assays (FITC-Dextran, DAO, D-lactate), in vitro LPS-treated enteroids, histopathology FASEB journal Medium 38651689
2010 Deletion of the PPARγ binding site (PPARE) in the Pck1 promoter reduces fasting Pck1 mRNA in white and brown adipose tissue, causing profound insulin resistance (measured by hyperinsulinemic-euglycemic clamp) with increased FFA and glycerol release, and a 2-fold increase in insulin secretion. This establishes that Pck1 in adipose tissue is required for normal lipid metabolism and glucose homeostasis via glyceroneogenesis. PPARE(-/-) mice, hyperinsulinemic-euglycemic clamp, isolated islet insulin secretion assay, gene expression analysis Journal of lipid research High 20124556
2024 T3 (thyroid hormone) and glucose coordinately regulate PCK1 expression in β-cells via ChREBPβ. The thyroid hormone receptor (THR) and ChREBP interact (confirmed by proximity ligation assay and ChIP), and their response elements are co-located on target genes. Overexpression of Pck1 together with a substrate precursor (dimethyl malate) significantly increased β-cell proliferation in human islets, and ChREBPβ contributes to Pck1-dependent β-cell proliferation. RNA-seq of human islets, ChIP, proximity ligation assay (THR-ChREBP), PCK1 overexpression with substrate, Cre-Lox ChREBPβ deletion, ki67 proliferation staining Molecular metabolism Medium 36455788
2004 The -232C→G promoter SNP in PCK1 falls within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription. A luciferase reporter construct containing -232G showed significantly increased basal expression and no down-regulation by insulin compared to -232C, establishing that this element mediates insulin-dependent repression of PCK1. Luciferase reporter assay in three cell lines, promoter sequencing, association study The Journal of clinical endocrinology and metabolism Medium 14764811
2016 Neonatal re-expression of PCK1 in the liver of whole-body PEPCK-C knockout mice by adenoviral delivery was sufficient to partially rescue hypoglycemia and allow pups to survive, establishing that liver PCK1 is the critical determinant of the lethal hypoglycemic phenotype in whole-body knockouts. Adenoviral liver-specific PCK1 re-expression in whole-body KO pups, blood glucose measurements, survival analysis Journal of physiology and biochemistry Medium 27785616
2024 SIRT2 prevents PCK1 degradation (via deacetylation, stabilizing the protein) in chondrocytes. PCK1 overexpression inhibits Wnt/β-catenin signaling, reduces inflammatory factor levels, ECM degradation (MMP-13), and apoptosis in IL-1β-treated chondrocytes. SIRT2 overexpression rescued the pro-inflammatory effects of PCK1 silencing, establishing SIRT2 as an upstream stabilizer of PCK1. Overexpression and knockdown of SIRT2 and PCK1 in chondrocytes, ELISA for cytokines, western blotting for Wnt/β-catenin pathway, apoptosis assays Discovery medicine Low 39463224
2024 PRRSV infection activates AKT, which then activates PCK1. Activated PCK1 phosphorylates INSIG proteins, causing their degradation, which allows SCAP-SREBP translocation from the ER to the nucleus and activation of lipid biosynthesis. ROS produced by PRRSV activates AKT upstream of PCK1. MARC-145 cell infection, metabolic analysis, AKT/PCK1/INSIG western blotting, SREBPs nuclear translocation assay, ROS measurement International journal of biological macromolecules Medium 39433189

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 293 32322062
2017 A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells. Nature cell biology 178 29230018
2018 Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma. Oncogene 167 29335519
2007 PCK1 and PCK2 as candidate diabetes and obesity genes. Cell biochemistry and biophysics 164 17709878
2023 Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice. Nature communications 136 36918564
2008 Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice. Diabetes 113 18443203
2021 Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation. The Journal of clinical investigation 105 33690219
2004 Disregulated glyceroneogenesis: PCK1 as a candidate diabetes and obesity gene. Trends in endocrinology and metabolism: TEM 99 15046742
2018 Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway. Biochemical and biophysical research communications 91 29608893
2013 PEPCK-M expression in mouse liver potentiates, not replaces, PEPCK-C mediated gluconeogenesis. Journal of hepatology 87 23466304
2024 A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1. Cell metabolism 83 38718791
2010 Phosphoenolpyruvate carboxykinase (Pck1) helps regulate the triglyceride/fatty acid cycle and development of insulin resistance in mice. Journal of lipid research 82 20124556
2019 PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis. eLife 81 31841108
1997 Sequence and promoter regulation of the PCK1 gene encoding phosphoenolpyruvate carboxykinase of the fungal pathogen Candida albicans. Gene 80 9224895
2019 PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis. Journal of experimental & clinical cancer research : CR 69 30717766
2018 Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 67 29768256
2014 Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity. Molecular genetics and metabolism 56 24863970
2007 Candidate gene association study of insulin signaling genes and Alzheimer's disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 52 17440948
1992 Regulatory regions in the yeast FBP1 and PCK1 genes. FEBS letters 52 1327878
2023 Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression. The Journal of clinical investigation 51 37166978
2021 O-GlcNAc modified-TIP60/KAT5 is required for PCK1 deficiency-induced HCC metastasis. Oncogene 51 34650217
2016 The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to enhance the growth of hepatoma cells. Cancer letters 47 27609066
2018 PCK1 Downregulation Promotes TXNRD1 Expression and Hepatoma Cell Growth via the Nrf2/Keap1 Pathway. Frontiers in oncology 46 30619751
2004 Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus. The Journal of clinical endocrinology and metabolism 45 14764811
2023 PCK1 is a key regulator of metabolic and mitochondrial functions in renal tubular cells. American journal of physiology. Renal physiology 43 37102687
2023 PCK1 Protects against Mitoribosomal Defects in Diabetic Nephropathy in Mouse Models. Journal of the American Society of Nephrology : JASN 41 37199399
1995 Identification and characterization of regulatory elements in the phosphoenolpyruvate carboxykinase gene PCK1 of Saccharomyces cerevisiae. Molecular & general genetics : MGG 41 7854322
2019 Induction of Inflammatory Responses in Human Bronchial Epithelial Cells by Pb2+-Containing Model PM2.5 Particles via Downregulation of a Novel Long Noncoding RNA lnc-PCK1-2:1. Environmental science & technology 38 30913382
2018 Macrophages with a deletion of the phosphoenolpyruvate carboxykinase 1 (Pck1) gene have a more proinflammatory phenotype. The Journal of biological chemistry 38 29317502
2011 Insulin-regulated Srebp-1c and Pck1 mRNA expression in primary hepatocytes from zucker fatty but not lean rats is affected by feeding conditions. PloS one 35 21731709
2020 A newly discovered role of metabolic enzyme PCK1 as a protein kinase to promote cancer lipogenesis. Cancer communications (London, England) 34 32809272
2020 PCK1 Regulates Glycolysis and Tumor Progression in Clear Cell Renal Cell Carcinoma Through LDHA. OncoTargets and therapy 33 32280238
2014 Rho1 GTPase and PKC ortholog Pck1 are upstream activators of the cell integrity MAPK pathway in fission yeast. PloS one 33 24498240
2018 The key gluconeogenic gene PCK1 is crucial for virulence of Botrytis cinerea via initiating its conidial germination and host penetration. Environmental microbiology 29 29614212
2017 Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction. Molecular genetics and metabolism 29 28216384
2013 Androgen inhibits abdominal fat accumulation and negatively regulates the PCK1 gene in male chickens. PloS one 28 23544081
2020 Comparative transcriptome analysis reveals that PCK1 is a potential gene affecting IMF deposition in buffalo. BMC genomics 27 33045988
2017 Genistein represses PEPCK-C expression in an insulin-independent manner in HepG2 cells and in alloxan-induced diabetic mice. Journal of cellular biochemistry 27 28816409
2011 Berberine regulated Gck, G6pc, Pck1 and Srebp-1c expression and activated AMP-activated protein kinase in primary rat hepatocytes. International journal of biological sciences 27 21647250
2000 Differences in regulation of yeast gluconeogenesis revealed by Cat8p-independent activation of PCK1 and FBP1 genes in Kluyveromyces lactis. Molecular & general genetics : MGG 27 11016849
2019 Rev-erbα activation down-regulates hepatic Pck1 enzyme to lower plasma glucose in mice. Pharmacological research 26 30639375
2009 The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population. BMC medical genetics 25 19725958
1993 cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young. Human molecular genetics 25 8490617
2022 PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities. Genes & diseases 24 37013052
2011 Retinoids induced Pck1 expression and attenuated insulin-mediated suppression of its expression via activation of retinoic acid receptor in primary rat hepatocytes. Molecular and cellular biochemistry 24 21519922
2007 Liver lipid molecules induce PEPCK-C gene transcription and attenuate insulin action. Biochemical and biophysical research communications 24 17678617
1993 Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics 24 8325643
2015 Translocation of forkhead box O1 to the nuclear periphery induces histone modifications that regulate transcriptional repression of PCK1 in HepG2 cells. Genes to cells : devoted to molecular & cellular mechanisms 22 25736587
2023 hnRNPA2B1 promotes the occurrence and progression of hepatocellular carcinoma by downregulating PCK1 mRNA via a m6A RNA methylation manner. Journal of translational medicine 20 38017546
2020 Hepatocellular carcinoma cell-derived extracellular vesicles encapsulated microRNA-584-5p facilitates angiogenesis through PCK1-mediated nuclear factor E2-related factor 2 signaling pathway. The international journal of biochemistry & cell biology 20 32522621
2014 Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression. PloS one 20 24586865
1996 Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on chromosome 20q to non-insulin-dependent diabetes mellitus. Diabetes & metabolism 20 8985654
2019 Relationships of SLC2A4, RBP4, PCK1, and PI3K Gene Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population. BioMed research international 19 30805369
2016 c.A2456C-substitution in Pck1 changes the enzyme kinetic and functional properties modifying fat distribution in pigs. Scientific reports 19 26792594
2016 Gentiopicroside and sweroside from Veratrilla baillonii Franch. induce phosphorylation of Akt and suppress Pck1 expression in hepatoma cells. Biochemistry and cell biology = Biochimie et biologie cellulaire 19 27248905
2016 PEPCK-C reexpression in the liver counters neonatal hypoglycemia in Pck1 del/del mice, unmasking role in non-gluconeogenic tissues. Journal of physiology and biochemistry 19 27785616
2023 Hepatic retinaldehyde deficiency is involved in diabetes deterioration by enhancing PCK1- and G6PC-mediated gluconeogenesis. Acta pharmaceutica Sinica. B 18 37719384
2016 Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep. American journal of physiology. Regulatory, integrative and comparative physiology 18 27170658
2023 m 6 A-mediated gluconeogenic enzyme PCK1 upregulation protects against hepatic ischemia-reperfusion injury. Hepatology (Baltimore, Md.) 17 38085830
2005 Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits. Stroke 17 16282543
2010 A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis. PloS one 16 21152065
1993 Human PCK1 encoding phosphoenolpyruvate carboxykinase is located on chromosome 20q13.2. Genomics 16 8432541
2022 Nintedanib Alleviates Experimental Colitis by Inhibiting CEBPB/PCK1 and CEBPB/EFNA1 Pathways. Frontiers in pharmacology 15 35910380
2024 PCK1-mediated glycogenolysis facilitates ROS clearance and chemotherapy resistance in cervical cancer stem cells. Scientific reports 13 38871968
2024 Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs axis. International journal of biological macromolecules 13 39433189
1995 Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. Genetical research 13 7781998
2024 Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 38651689
2023 Role of phosphoenolpyruvate carboxykinase 1 (pck1) in mediating nutrient metabolism in zebrafish. Functional & integrative genomics 12 36840800
2020 Novel missense variants in PCK1 gene cause cytosolic PEPCK deficiency with growth failure from inadequate caloric intake. Journal of human genetics 12 32908218
1992 The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2. Annals of human genetics 12 1492743
2016 PCK1 is negatively regulated by bta-miR-26a, and a single-nucleotide polymorphism in the 3' untranslated region is involved in semen quality and longevity of Holstein bulls. Molecular reproduction and development 11 26725319
2006 Association of the promoter polymorphism -232C/G of the phosphoenolpyruvate carboxykinase gene (PCK1) with Type 2 diabetes mellitus. Diabetic medicine : a journal of the British Diabetic Association 11 16620271
2021 PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer. British journal of cancer 10 34815524
2019 Transcriptomic changes associated with PCK1 overexpression in hepatocellular carcinoma cells detected by RNA-seq. Genes & diseases 10 32181286
2025 Positively Charged Nanoplastics Destruct the Structure of the PCK1 Enzyme, Promote the Aerobic Gycolysis Pathway, and Induce Hepatic Tumor Risks. Environmental science & technology 9 39907589
2024 PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling. Cell death discovery 9 39578429
2023 PCK1 activates oncogenic autophagy via down-regulation Serine phosphorylation of UBAP2L and antagonizes colorectal cancer growth. Cancer cell international 9 37062825
2022 NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression. Frontiers in cell and developmental biology 9 36092708
2022 T3 and glucose increase expression of phosphoenolpyruvate carboxykinase (PCK1) leading to increased β-cell proliferation. Molecular metabolism 9 36455788
2019 Role of PCK1 gene on oil tea-induced glucose homeostasis and type 2 diabetes: an animal experiment and a case-control study. Nutrition & metabolism 9 30805021
2008 [Glyceroneogenesis and PEPCK-C: pharmacological targets in type 2 diabetes]. Medecine sciences : M/S 9 18405640
2020 PCK1 Deficiency Shortens the Replicative Lifespan of Saccharomyces cerevisiae through Upregulation of PFK1. BioMed research international 8 32104690
2010 Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS). Obesity (Silver Spring, Md.) 8 20134411
2008 Identification of conserved regulatory elements in mammalian promoter regions: a case study using the PCK1 promoter. Genomics, proteomics & bioinformatics 8 19329064
2006 Large-scale study of the -232C > G polymorphism of PCK1 in Type 2 diabetes. Diabetic medicine : a journal of the British Diabetic Association 8 16978381
2025 PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion. The Journal of experimental medicine 7 40048154
2024 SIRT2 Alleviates Inflammatory Response, Apoptosis, and ECM Degradation in Osteoarthritic Chondrocytes by Stabilizing PCK1. Discovery medicine 7 39463224
2023 SHP-1 phosphatase acts as a coactivator of PCK1 transcription to control gluconeogenesis. The Journal of biological chemistry 7 37595871
2021 Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity. The Journal of biological chemistry 7 33334880
2017 PCK1 expression is correlated with the plasma glucose level in the duck. Animal genetics 7 28198082
2015 Phosphoenolpyruvate carboxykinase 1 gene (Pck1) displays parallel evolution between Old World and New World fruit bats. PloS one 7 25807515
2008 A Leu184Val polymorphism in PCK1 gene is associated with type 2 diabetes in Eastern Chinese population with BMI<23 kg/m2. Diabetes research and clinical practice 6 19070910
2024 Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis. The pharmacogenomics journal 5 38378770
2024 Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation. Cell chemical biology 5 39341205
2024 Integrated hepatic transcriptomics and metabolomics identify Pck1 as a key factor in the broad dysregulation induced by vehicle pollutants. Particle and fibre toxicology 5 39734207
2023 Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer. Biochemistry and biophysics reports 5 37637941
2021 Chronic AT1 blockade improves hyperglycemia by decreasing adipocyte inflammation and decreasing hepatic PCK1 and G6PC1 expression in obese rats. American journal of physiology. Endocrinology and metabolism 5 34658252
2019 Knockdown of the Sonic Hedgehog (SHH) Gene Inhibits Proliferation of Hep3B and SMMC-7721 Hepatocellular Carcinoma Cells via the PI3K/Akt/PCK1 Signaling Pathway. Medical science monitor : international medical journal of experimental and clinical research 5 31406102
2019 Recognition of the gluconeogenic enzyme, Pck1, via the Gid4 E3 ligase: An in silico perspective. Journal of molecular recognition : JMR 5 31883179
2013 Novel splice variants of the bovine PCK1 gene. Genetics and molecular research : GMR 5 24089092

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