Affinage

PKM

Pyruvate kinase PKM · UniProt P14618

Length
531 aa
Mass
57.9 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 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

PKM (PKM2 isoform) is a multifunctional glycolytic pyruvate kinase whose tetrameric form drives metabolic flux but whose dimeric/monomeric forms acquire non-canonical activities upon translocation to the nucleus, coordinating metabolism with gene expression, cell-cycle control, and inflammation (PMID:22056988, PMID:24316223). The interconversion between oligomeric states is the central regulatory switch: tetramerization favors enzymatic pyruvate kinase activity, whereas dimer/monomer formation favors nuclear functions, and this balance is tuned by an extensive set of post-translational modifications including lactylation at K62 (PMID:36439872), palmitoylation at C31 (PMID:39665133), glutathionylation at Cys423/424 (PMID:36815040), sumoylation (PMID:36116159), and several ubiquitin linkages (PMID:40079144). In the nucleus, PKM2 acts as a co-transcriptional activator that binds c-Src-phosphorylated β-catenin to drive CCND1 transcription (PMID:22056988), and phosphorylates histone H3 at T11 to evict HDAC3 and activate cyclin D1 and c-Myc (PMID:22901803, PMID:36899022). During mitosis it phosphorylates the spindle-checkpoint protein Bub3 at Y207 to ensure correct kinetochore-microtubule attachment (PMID:24316223), and during cytokinesis Aurora-B-primed PKM2 phosphorylates MLC2 at Y118 at the contractile ring (PMID:25412762); it also moonlights as a PEP-dependent histidine kinase phosphorylating PGAM1 at H11 (PMID:38750259). Nuclear PKM2 additionally functions as a non-canonical RNA-binding protein that occupies RNA G-quadruplex structures in pre-mRNAs to promote their expression and cancer cell invasion (PMID:39153475), and binds ribosomes in a PARylation- and ADP-dependent manner to stall translation (PMID:37224531). Through nuclear partnership with STAT3 and NF-κB, PKM2 controls Th17 differentiation, macrophage and neutrophil inflammatory programs, and tumor angiogenesis (PMID:32697823, PMID:34529778, PMID:33314660). PKM2 abundance is governed by chaperone-mediated autophagy following K305 acetylation or Jmjd4-catalyzed K66 hydroxylation (PMID:22096030, PMID:37066795). An in vitro reconstitution study using [32P]-PEP failed to detect PKM2-dependent protein kinase activity, defining a point of contention over the protein-kinase model (PMID:26300261).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2011 High

    Established that PKM2, unlike PKM1, has a nuclear non-metabolic role by showing growth-signal-induced nuclear translocation and a direct interaction with β-catenin required for oncogenic transcription, reframing a metabolic enzyme as a transcriptional coactivator.

    Evidence Co-IP, ChIP, nuclear fractionation, K433/Y333 mutagenesis, and in vivo brain tumor models

    PMID:22056988

    Open questions at the time
    • Did not resolve how PKM2 oligomeric state controls nuclear entry
    • Structural basis of the PKM2-β-catenin interface not defined
  2. 2011 Medium

    Linked a specific PTM to PKM2 turnover by showing K305 acetylation lowers enzymatic activity and routes PKM2 to chaperone-mediated autophagy, connecting acetylation status to enzyme abundance.

    Evidence In vitro activity assay, acetylation mutant analysis, lysosomal/CMA degradation assays

    PMID:22096030

    Open questions at the time
    • Abstract-level detail only
    • Acetyltransferase and deacetylase not defined in this study
  3. 2012 High

    Provided the first proposed protein-kinase mechanism for nuclear PKM2 by demonstrating direct histone H3-T11 phosphorylation that evicts HDAC3 to activate cyclin D1 and c-Myc, defining an epigenetic output of PKM2.

    Evidence In vitro kinase assay with recombinant proteins, Co-IP, ChIP, mass spectrometry, mutagenesis, in vivo tumor models

    PMID:22901803

    Open questions at the time
    • Phosphate-donor mechanism (PEP vs ATP) not definitively resolved
    • Later challenged by negative reconstitution data
  4. 2013 High

    Extended the PKM2 protein-kinase model to mitosis by showing isoform-specific phosphorylation of Bub3 at Y207 controls kinetochore attachment and spindle-checkpoint fidelity, implicating PKM2 in chromosome segregation.

    Evidence Co-IP, in vitro kinase assay, Y207 mutagenesis, kinetochore imaging, rescue and in vivo tumor models

    PMID:24316223

    Open questions at the time
    • Phosphotransfer chemistry not independently confirmed
    • How mitotic PKM2 is targeted to kinetochores unclear
  5. 2014 High

    Connected upstream mitotic kinase signaling to PKM2 localization, showing Aurora B phosphorylation at T45 directs PKM2 to the contractile ring where it primes MLC2 for ROCK2, integrating PKM2 into cytokinesis.

    Evidence In vitro kinase assays, Co-IP, T45/Y118 mutagenesis, live-cell imaging, in vivo tumor models

    PMID:25412762

    Open questions at the time
    • Generality beyond tumor models not established
    • Does not resolve the broader controversy over PKM2 kinase activity
  6. 2015 High

    Directly challenged the PKM2 protein-kinase paradigm by failing to detect PKM2-dependent protein phosphorylation in reconstituted [32P]-PEP assays with genetic deletion controls, defining a methodological dispute central to the field.

    Evidence Radioisotope [32P]-PEP labeling with recombinant PKM2 and PKM2-deleted cell systems

    PMID:26300261

    Open questions at the time
    • Negative result does not exclude context-dependent kinase activity in cells
    • Does not reconcile with positive reconstitution reports
  7. 2016 High

    Established a metabolism-driven role for PKM2 in innate immunity, showing glycolytic PKM2 promotes inflammasome activation via EIF2AK2 and that myeloid PKM2 loss protects against sepsis.

    Evidence Myeloid-specific conditional knockout, pharmacological inhibition, inflammasome and cytokine assays, in vivo sepsis models

    PMID:27779186

    Open questions at the time
    • Whether the effect is purely metabolic or involves nuclear PKM2 not dissected
    • Direct PKM2-EIF2AK2 biochemistry not shown
  8. 2019 Medium

    Identified a direct mitochondrial partner, showing PKM2-MFN2 interaction promotes fusion and OXPHOS while restraining glycolysis under mTOR control, establishing PKM2 as a node balancing glycolysis and respiration.

    Evidence Co-IP, mitochondrial imaging, Seahorse flux, mTOR inhibitor and genetic manipulation

    PMID:30887444

    Open questions at the time
    • No structural validation of the interaction
    • Single lab; reciprocal validation limited
  9. 2020 High

    Demonstrated a metabolism-independent nuclear function in adaptive immunity, where PKM2-STAT3 interaction drives Th17 differentiation independent of metabolic reprogramming.

    Evidence T cell-specific conditional knockout, PKM2-STAT3 Co-IP, flow cytometry, EAE model

    PMID:32697823

    Open questions at the time
    • Direct vs indirect enhancement of STAT3 not fully separated
    • Oligomeric state required for STAT3 binding not defined
  10. 2020 Medium

    Extended PKM2 cell-cycle and redox functions to developmental physiology, showing cardiomyocyte PKM2 supports proliferation and limits oxidative stress via β-catenin during heart development.

    Evidence Cardiomyocyte-specific conditional knockout, modified mRNA overexpression, morphometry, MI models

    PMID:32078387

    Open questions at the time
    • Limited orthogonal biochemical validation of the β-catenin link
    • Mechanism of oxidative-stress reduction not detailed
  11. 2021 Medium

    Defined an extracellular, receptor-mediated PKM2 function, where secreted PKM2 engages integrin αvβ3 to activate FAK-PI3K-NF-κB survival and pro-fibrotic collagen synthesis.

    Evidence Co-IP of EcPKM2-integrin, FAK-PI3K assays, NF-κB reporter, antibody blocking, in vivo fibrosis models

    PMID:34693222

    Open questions at the time
    • Mechanism of PKM2 secretion not defined
    • Single lab; structural basis of integrin binding unknown
  12. 2021 Medium

    Broadened nuclear partner repertoire by showing PKM2-NF-κB complexes (importin-4-dependent) drive VEGFA transcription and that an FBP-induced FOXM1D-PKM2 heterooctamer suppresses metabolic activity, linking oligomerization to angiogenesis.

    Evidence Co-IP, nuclear fractionation, importin-4 knockdown, VEGFA reporter, metabolic assays, angiogenesis model

    PMID:33314660

    Open questions at the time
    • Heterooctamer stoichiometry not structurally resolved
    • Single lab
  13. 2022 Medium

    Identified lactylation at K62 as a PTM that locks PKM2 in its tetramer, raising enzymatic activity and reducing nuclear distribution to reprogram macrophage phenotype, formalizing a PTM-oligomer-function axis.

    Evidence Mass spectrometry, K62 mutagenesis, activity assay, native PAGE, nuclear fractionation, polarization assays

    PMID:36439872

    Open questions at the time
    • Enzyme catalyzing K62 lactylation not defined
    • Single lab
  14. 2022 Medium

    Showed multiple PTM and binding-partner routes converge on the tetramer-dimer equilibrium: sumoylation (GTPBP4-SUMO1) and CXCL12-driven β-arrestin-2/ERK2 interactions favor dimers/nuclear PKM2, while Annexin A5 binding and CoA binding favor tetramers and block nuclear translocation.

    Evidence Co-IP, sumoylation and oligomerization assays, pull-down with residue mapping, metabolite tracing, binding assays, immune/tumor models

    PMID:32863213 PMID:35681470 PMID:36116159 PMID:36450257

    Open questions at the time
    • These regulators were studied in separate systems and not integrated
    • Quantitative hierarchy of competing inputs unknown
  15. 2022 Medium

    Defined pharmacological and lipid-based covalent control of PKM2 activity, with celastrol binding Cys424 and zDHHC13-mediated C31 palmitoylation both impairing tetramerization and activity in inflammatory and vascular disease contexts.

    Evidence ABPP, CETSA, SPR, palmitoyl-proteomics, C31S/Cys424 mutagenesis, activity and native PAGE assays, in vivo models

    PMID:35596191 PMID:39665133

    Open questions at the time
    • Off-target effects of celastrol not fully excluded
    • Interplay between palmitoylation and other C31-proximal modifications unknown
  16. 2022 Medium

    Linked PKM2 abundance and isoform choice to vascular and fibrotic disease through ubiquitin regulation (JOSD2 deubiquitinase blocks K433 acetylation/nuclear entry; FSTL1 reduces ubiquitination to enhance nuclear PKM2) and splicing control (PHB2-hnRNPA1 axis sets PKM2 expression).

    Evidence Co-IP, mass spectrometry, ubiquitination and acetylation assays, mammalian two-hybrid, splicing RT-PCR, genetic KO models

    PMID:35140065 PMID:35836282 PMID:36200440

    Open questions at the time
    • Reciprocal validation of some interactions limited
    • Single-lab studies
  17. 2022 Medium

    Showed a redox-sensing nuclear function in which ROS-induced Cys423/424 glutathionylation drives dimer/monomer nuclear translocation where PKM2 acts as a HIF-1α cofactor for cardioprotective gene induction.

    Evidence Cys423/424 mutagenesis, glutathionylation assay, nuclear fractionation, HIF-1α reporter, cardiac knockdown, ischemia model

    PMID:36815040

    Open questions at the time
    • Direct HIF-1α cofactor mechanism not biochemically detailed
    • Single lab
  18. 2023 High

    Resolved a degradation mechanism by showing Jmjd4-catalyzed K66 hydroxylation, together with Hsp70, routes PKM2 to chaperone-mediated autophagy, with loss causing PKM2 accumulation and dilated cardiomyopathy.

    Evidence Cardiomyocyte-specific Jmjd4 knockout, Jmjd4-Hsp70-PKM2 Co-IP, mass spectrometry, CMA assays, metabolite profiling

    PMID:37066795

    Open questions at the time
    • How hydroxylation creates a CMA-targeting signal not structurally defined
    • Generality beyond cardiomyocytes untested
  19. 2023 High

    Connected serine-pathway metabolism to PKM2 stability and nuclear function, showing PHGDH binding blocks K305 acetylation/autophagy while promoting p300-mediated K433 acetylation, nuclear entry, and H3T11 phosphorylation governing senescence genes.

    Evidence Co-IP, K305/K433 mutagenesis, in vitro H3T11 kinase assay, autophagy inhibition, ChIP, endothelial senescence models

    PMID:36899022

    Open questions at the time
    • Reconciliation with negative protein-kinase data not addressed
    • Direct PHGDH-PKM2 interface not structurally mapped
  20. 2023 High

    Established PKM2 as a metabolism-responsive translational regulator, showing PARylation- and ADP-dependent ribosome binding and crosslinking to codon-specific mRNA regions that stall translation, coupling carbohydrate metabolism to protein synthesis.

    Evidence Polysome proteomics, eCLIP-seq, ribosome footprint profiling, ADP titration, PARylation inhibition

    PMID:37224531

    Open questions at the time
    • Direct RNA-binding interface on PKM2 not defined
    • Physiological consequences of stalling not fully mapped
  21. 2024 High

    Defined a moonlighting histidine-kinase activity in which monomeric/dimeric PKM2 phosphorylates PGAM1 H11 (PEP-dependent, primed by Src Y119 phosphorylation), tying PKM2 oligomeric state to a specific glycolytic substrate.

    Evidence In vitro histidine kinase assay, mass spectrometry, Co-IP, H11/Y119 mutagenesis, peptide disruption, xenografts

    PMID:38750259

    Open questions at the time
    • Independent reconstitution in light of prior negative kinase data lacking
    • Chemistry of histidine phosphotransfer not structurally resolved
  22. 2024 High

    Identified a sequence-specific non-canonical RNA function, showing nuclear PKM2 binds RNA G-quadruplexes in pre-mRNAs to exclude repressive RBPs like HNRNPF and promote rG4-containing transcript expression and invasion.

    Evidence eCLIP-seq, ribosome footprinting, in vitro G-quadruplex binding, nuclear fractionation, HNRNPF competition, xenografts

    PMID:39153475

    Open questions at the time
    • RNA-binding domain/residues of PKM2 not mapped
    • Relationship to PKM2 kinase activity unknown
  23. 2024 Medium

    Showed SIRT1 deacetylates PKM2 at K135/K206 to lower enzymatic activity and lactate, reducing glial activation in Parkinson's disease models, adding a deacetylation node to PKM2 regulation.

    Evidence Co-IP, K135/K206 site mapping, activity and lactate assays, PD mouse models with SIRT1 and PKM2 manipulation

    PMID:39128469

    Open questions at the time
    • Single lab
    • Whether deacetylation affects oligomeric state not addressed
  24. 2024 Medium

    Demonstrated that PKM2 aggregation in senescent and aged tissues impairs its enzymatic activity and glycolysis to drive senescence, and that dissolving aggregates extends lifespan, linking PKM2 conformational state to aging.

    Evidence Aggregate detection, activity assays, small-molecule screening, senescence markers, lifespan measurement

    PMID:38982055

    Open questions at the time
    • Structural nature of aggregates undefined
    • Single lab
  25. 2025 Medium

    Identified additional ubiquitin- and phospho-based tetramer-promoting inputs (PINK1 S127 phosphorylation; March2 K33-linked ubiquitination) that block nuclear translocation and constrain glycolysis-derived histone lactylation in osteoarthritis and aortic disease.

    Evidence Genetic KO/overexpression models, Co-IP, S127 phosphorylation and K33-ubiquitination analysis, native PAGE, CUT&TAG, pharmacological rescue

    PMID:40079144 PMID:40087281

    Open questions at the time
    • Single-lab studies
    • How distinct ubiquitin linkages mechanistically alter oligomerization not resolved
  26. 2025 Medium

    Extended PKM2-derived lactate to developmental epigenetics and immune metabolite signaling, with H3K9 lactylation controlling Sox factors in cochlear development and tetramer-driven ATP/adenosine-A2aR signaling enhancing macrophage IL-10.

    Evidence Conditional KO, organoids, H3K9la ChIP, metabolic flux, TEPP-46 activation, ATP/adenosine measurement, A2aR antagonism, IL-10 ELISA

    PMID:39772395 PMID:39773029

    Open questions at the time
    • Direct vs metabolite-mediated effects not fully separated in all contexts
    • Single-lab studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central unresolved question remains whether PKM2's reported protein/histidine kinase activities reflect a genuine intrinsic catalytic mechanism or are artifacts/indirect effects, and how a single quaternary-structure equilibrium is quantitatively partitioned among its glycolytic, kinase, transcriptional, RNA-binding, and translational roles in a given cell.
  • Positive (H3T11, Bub3, MLC2, PGAM1) and negative reconstitution results not reconciled
  • No unified structural model linking oligomeric state to each non-canonical activity
  • Quantitative flux partitioning among competing functions unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 2 GO:0016740 transferase activity 2
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 3 GO:0005576 extracellular region 1 GO:0005739 mitochondrion 1 GO:0005840 ribosome 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-9612973 Autophagy 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ANXA5CTNNB1FSTL1MARCH2MFN2PGAM1PHGDHSTAT3

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 EGFR activation induces translocation of PKM2 (but not PKM1) into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of β-catenin. This PKM2–β-catenin interaction is required for recruitment to the CCND1 promoter, HDAC3 removal, histone H3 acetylation, and cyclin D1 expression, thereby promoting tumor cell proliferation. Co-immunoprecipitation, chromatin immunoprecipitation, nuclear fractionation, site-directed mutagenesis (K433, Y333), gene reporter assays, in vivo brain tumor models Nature High 22056988
2012 Nuclear PKM2 directly binds histone H3 and phosphorylates it at T11 upon EGF receptor activation. This phosphorylation causes dissociation of HDAC3 from the CCND1 and MYC promoters, leading to H3K9 acetylation and transcriptional activation of cyclin D1 and c-Myc, promoting cell-cycle progression and tumorigenesis. In vitro kinase assay with recombinant proteins, Co-IP, ChIP, mass spectrometry, site-directed mutagenesis, in vivo brain tumor models Cell High 22901803
2013 PKM2 (but not PKM1) binds the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at Y207. This phosphorylation is required for Bub3-Bub1 complex recruitment to kinetochores, correct kinetochore-microtubule attachment, mitotic/spindle-assembly checkpoint fidelity, and accurate chromosome segregation. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Y207), kinetochore localization imaging, genetic rescue experiments, in vivo tumor models Molecular cell High 24316223
2014 Aurora B phosphorylates PKM2 (but not PKM1) at T45, which is required for PKM2 localization to the contractile ring during cytokinesis. PKM2 then phosphorylates MLC2 at Y118, priming ROCK2 binding to MLC2 and subsequent ROCK2-dependent MLC2 S15 phosphorylation, driving cytokinesis completion and cell proliferation. In vitro kinase assay, Co-IP, site-directed mutagenesis (T45, Y118), live-cell imaging, mass spectrometry, in vivo brain tumor models Nature communications High 25412762
2011 Acetylation of PKM2 at Lys305 decreases its pyruvate kinase activity and targets it for chaperone-mediated autophagy and subsequent lysosomal degradation. In vitro enzymatic activity assay, acetylation mutant analysis, lysosomal degradation assays, chaperone-mediated autophagy pathway analysis Cold Spring Harbor symposia on quantitative biology Medium 22096030
2015 Using [32P]-phosphoenolpyruvate (PEP) with recombinant enzyme and PKM2-deleted in vitro systems, no PKM2-dependent protein kinase activity was detected; labeled protein species required ADP and were not PKM2-dependent, and direct phosphate transfer from ATP to protein by PKM2 was not observed. This constitutes a NEGATIVE finding challenging PKM2 protein kinase activity. Radioisotope [32P]-PEP labeling assay with recombinant PKM2, genetic deletion of PKM2 in cell systems, in vitro phosphorylation assays Molecular cell High 26300261
2016 PKM2-mediated glycolysis promotes NLRP3 and AIM2 inflammasome activation in macrophages by modulating EIF2AK2 phosphorylation. Myeloid cell-specific conditional knockout of PKM2 attenuates inflammasome activation and protects mice from lethal endotoxemia and polymicrobial sepsis. Myeloid-specific PKM2 conditional knockout mice, pharmacological inhibition, inflammasome activation assays, cytokine measurement, in vivo sepsis models Nature communications High 27779186
2019 PKM2 interacts with mitofusin 2 (MFN2) to promote mitochondrial fusion and oxidative phosphorylation while attenuating glycolysis. mTOR modulates this interaction by phosphorylating MFN2, establishing an mTOR-MFN2-PKM2 signaling axis that coordinates glycolysis and OXPHOS. Co-immunoprecipitation, mitochondrial morphology imaging, metabolic flux analysis (Seahorse), mTOR inhibitor experiments, genetic manipulation of MFN2 and PKM2 Protein & cell Medium 30887444
2020 PKM2 translocates into the nucleus in Th17 cells and interacts with STAT3, enhancing STAT3 activation and thereby promoting Th17 cell differentiation. T cell-specific PKM2 deletion impairs Th17 differentiation and ameliorates experimental autoimmune encephalomyelitis, independent of effects on metabolic reprogramming or proliferation. T cell-specific PKM2 conditional knockout, Co-immunoprecipitation of PKM2-STAT3, flow cytometry for Th17 markers, EAE mouse model The Journal of experimental medicine High 32697823
2022 Lactylation of PKM2 at K62 inhibits its tetramer-to-dimer transition, thereby promoting its pyruvate kinase activity and reducing nuclear distribution, which suppresses the Warburg effect and promotes transition of pro-inflammatory macrophages toward a reparative phenotype. Mass spectrometry identification of lactylation site, K62 mutant analysis, pyruvate kinase activity assay, native PAGE for tetramer/dimer analysis, nuclear fractionation, macrophage polarization assays International journal of biological sciences Medium 36439872
2020 PKM2 regulates the cardiomyocyte cell cycle and reduces oxidative stress through anabolic pathways and β-catenin. Cardiomyocyte-specific Pkm2 deletion during cardiac development reduces cardiomyocyte cell cycle activity, cardiomyocyte numbers, and myocardial size. Cardiomyocyte-specific Pkm2 conditional knockout, modified mRNA overexpression, cardiac morphometry, cell cycle marker analysis, myocardial infarction models Circulation Medium 32078387
2023 PHGDH prevents PKM2 K305 acetylation (catalyzed by PCAF) and subsequent autophagic degradation by directly interacting with PKM2. PHGDH also facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and enables it to phosphorylate H3T11, regulating transcription of senescence-associated genes. Co-immunoprecipitation, acetylation mutant analysis (K305, K433), in vitro kinase assay (H3T11 phosphorylation), autophagy inhibition assays, ChIP, endothelial senescence models Nature communications High 36899022
2023 Jmjd4 interacts with Hsp70 to mediate degradation of Pkm2 through chaperone-mediated autophagy, dependent on Jmjd4-catalyzed hydroxylation of K66 of Pkm2. Loss of Jmjd4 in cardiomyocytes leads to Pkm2 accumulation, impaired mitochondrial respiration, and spontaneous dilated cardiomyopathy. Cardiomyocyte-specific Jmjd4 conditional knockout, Co-IP of Jmjd4-Hsp70-Pkm2, mass spectrometry, chaperone-mediated autophagy assays, metabolite profiling, RNA-seq Circulation High 37066795
2024 SIRT1 interacts with and deacetylates PKM2 at K135 and K206, leading to reduced PKM2 enzymatic activity and lactate production, which decreases glial activation in the brain and ameliorates Parkinson's disease phenotypes. Co-immunoprecipitation, deacetylation site mapping (K135, K206), pyruvate kinase activity assay, lactate measurement, PD mouse models with SIRT1 knockdown/overexpression and PKM2 inhibition Cell reports. Medicine Medium 39128469
2024 PKM2 moonlights as a histidine kinase in a phosphoenolpyruvate (PEP)-dependent manner to catalyze PGAM1 H11 phosphorylation, which is essential for PGAM1 activity. Monomeric and dimeric PKM2 (but not tetrameric) efficiently phosphorylate PGAM1. Src-catalyzed PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and subsequent H11 phosphorylation. In vitro histidine kinase assay, mass spectrometry, Co-IP, site-directed mutagenesis (H11, Y119), cell-permeable peptide disruption of PKM2-PGAM1 interaction, tumor xenograft models The EMBO journal High 38750259
2024 Nuclear PKM2 functions as a non-canonical RNA-binding protein that specifically interacts with folded RNA G-quadruplex (rG4) structures in precursor mRNAs. PKM2 occupancy at rG4s prevents binding of repressive RBPs (e.g., HNRNPF) and promotes expression of rG4-containing pre-mRNAs. Preventing nuclear PKM2 accumulation represses the rG4ome and reduces cancer cell migration and invasion. eCLIP-seq, ribosome footprinting, nuclear fractionation, RNA-binding assays, in vitro G-quadruplex binding, xenograft mouse models, competitive displacement with HNRNPF Molecular cell High 39153475
2023 PKM binds ribosomes in a poly-ADP ribosylation (PARylation)-dependent manner. PKM crosslinks to mRNA sequences downstream of lysine- and glutamate-encoding regions and causes translational stalling near these sequences. PKM-polysome interaction is regulated by ADP levels, linking carbohydrate metabolism to mRNA translation regulation. Proteomic polysome survey, eCLIP-seq, ribosome footprint protection sequencing, ADP titration assays, PARylation inhibition experiments Nucleic acids research High 37224531
2022 FSTL1 binds directly to PKM2 through its FK domain, promotes PKM2 phosphorylation and nuclear translocation, and reduces PKM2 ubiquitination, thereby enhancing PKM2-dependent glycolysis and macrophage M1 polarization, promoting liver fibrosis. Co-immunoprecipitation, nuclear fractionation, ubiquitination assay, myeloid-specific FSTL1 knockout mice, pharmacological PKM2 activation (DASA-58) Gut Medium 35140065
2020 Annexin A5 directly interacts with PKM2 at ASP101, LEU104, and ARG106, inhibits phosphorylation of Y105, and promotes PKM2 tetramer formation, thereby switching macrophage metabolism from glycolysis to oxidative phosphorylation and promoting M2 polarization. Pull-down assay, molecular docking, site-directed mutagenesis (D101, L104, R106), PKM2 Y105E phosphomimetic mutant, native PAGE for oligomeric state, metabolic flux analysis Redox biology Medium 32863213
2022 PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. Myeloid cell-specific PKM2 deletion reduced neutrophil extracellular traps, cerebral thrombo-inflammation, and infarct volume after stroke. Inhibiting PKM2 nuclear translocation pharmacologically reduced neutrophil hyperactivation. Myeloid-specific PKM2 conditional knockout mice, STAT3 phosphorylation assay, neutrophil extracellular trap quantification, stroke models (filament/clot), laser speckle imaging, small-molecule nuclear translocation inhibitor Blood High 34529778
2022 GTPBP4 facilitates SUMO1-mediated sumoylation of PKM2, which promotes PKM2 dimer formation and aerobic glycolysis. Sumoylated PKM2 relocates from cytoplasm to nucleus, activating EMT and STAT3 signaling in hepatocellular carcinoma. Co-immunoprecipitation, sumoylation assay, nuclear fractionation, UBA2 activation assay, gain/loss-of-function studies, in vitro and in vivo tumor models Redox biology Medium 36116159
2021 Extracellular PKM2 (EcPKM2) secreted by myofibroblasts interacts with integrin αvβ3 on myofibroblast surfaces to activate FAK-PI3K signaling, which activates NF-κB survival pathway (preventing apoptosis) and suppresses PTEN to upregulate arginase-1, facilitating proline biosynthesis and collagen production in organ fibrosis. Co-immunoprecipitation of EcPKM2-integrin αvβ3, FAK-PI3K phosphorylation assays, NF-κB reporter, arginase-1 assay, antibody blocking experiments, in vivo fibrosis models iScience Medium 34693222
2022 Celastrol binds covalently to Cys424 of PKM2, inhibiting its enzymatic activity and suppressing aerobic glycolysis (Warburg effect) in macrophages, thereby attenuating inflammatory responses in sepsis. Activity-based protein profiling (ABPP), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), point mutagenesis (Cys424), gene knockdown Military Medical Research Medium 35596191
2022 PKM2-C31 palmitoylation (mediated by palmitoyl acyltransferase zDHHC13) impairs PKM2 tetramerization, inhibits its pyruvate kinase activity and endothelial glycolysis, causing palmitic acid-induced endothelial injury and cardiovascular dysfunction. PKM2-C31S mutation prevents these effects. Palmitoyl-proteomics, site-directed mutagenesis (C31S), endothelial-specific AAV-mediated expression, pyruvate kinase activity assay, native PAGE for tetramerization, palmitoyl-transferase inhibitor/activator experiments, ApoE-/- mouse model Advanced science High 39665133
2022 Prohibitin 2 (PHB2), through its C-terminus, directly interacts with hnRNPA1 (a key modulator of PKM alternative splicing) to counteract hnRNPA1-mediated PKM2 expression and glycolysis, thereby maintaining the contractile VSMC phenotype. Co-immunoprecipitation, mammalian two-hybrid assay, protein interactome analysis, PKM splicing analysis (RT-PCR), metabolic flux analysis, PHB2-deficient mouse model, neointima formation model Circulation research Medium 36200440
2025 PINK1 phosphorylates PKM2 at Ser127, preserving its active tetrameric form and inhibiting its nuclear translocation and interaction with β-catenin, resulting in a metabolic shift toward energy production. SIRT3 deacetylates PINK1 to promote this pathway (SIRT3-PINK1-PKM2 axis) protecting against osteoarthritis. PINK1 knockout/overexpression mouse models, Co-immunoprecipitation, phosphorylation site analysis (S127), native PAGE for tetramer confirmation, nuclear fractionation, double-knockout mouse model Bone research Medium 40087281
2022 DEUBIQUITINASE JOSD2 interacts with PKM2 and reduces its K433 acetylation, thereby blocking PKM2 nuclear localization and downstream non-glycolytic gene expression in acute myeloid leukemia, without affecting PKM2 protein stability. Co-immunoprecipitation, mass spectrometry, co-immunofluorescence, K433 acetylation assay, nuclear fractionation, gene expression analysis, in vivo AML progression model Experimental hematology & oncology Medium 35836282
2025 March2 promotes K33-linked polyubiquitination of PKM2, facilitating PKM2 dimer-to-tetramer conversion. Deficiency of March2 lessens PKM2 tetramerization, promotes glycolysis-derived H3K18 lactylation, and drives p53-dependent apoptotic transcription, accelerating aortic aneurysm/dissection pathogenesis. Co-immunoprecipitation, ubiquitination type analysis (K33-linkage specific), native PAGE for oligomeric state, ChIP for H3K18 lactylation (CUT&TAG), smooth muscle cell-specific March2 knockout mice, PKM2 activator (TEPP-46) rescue Circulation research Medium 40079144
2025 PKM2-derived pyruvate is converted to lactate, which lactylates histone H3 at K9 (H3K9la), upregulating Sox family transcription factors through epigenetic modification to control cochlear development. PKM2 deletion causes a metabolic switch from glycolysis to OXPHOS and impairs cochlear sensory epithelium morphogenesis. Conditional PKM2 knockout in cochlear progenitors, cochlear organoids, H3K9la ChIP, metabolic flux analysis, gene expression (Sox factors), human and mouse cochlear explants with PKM2 overexpression Proceedings of the National Academy of Sciences of the United States of America Medium 39773029
2025 Tetrameric PKM2 (promoted by TEPP-46) increases ATP production from glycolysis; extracellular ATP is converted to adenosine via ectonucleotidases, activating adenosine receptor A2a (A2aR) to enhance IL-10 production in macrophages. This effect is abolished in PKM2-deficient macrophages. PKM2-deficient macrophages, TEPP-46 pharmacological activation, extracellular ATP/adenosine measurement, A2aR antagonist, ectonucleotidase inhibition, IL-10 ELISA, metabolic flux analysis Cell reports Medium 39772395
2022 PKM2 dimerization is induced by PKM2 sumoylation (via GTPBP4-SUMO1-UBA2 axis), and dimeric PKM2 promotes aerobic glycolysis and nuclear translocation. Separately, PKM2 nuclear translocation is required for complex formation with STAT3, HIF1α-mediated angiogenesis, and tumor maintenance in bladder cancer. PKM2 knockout, PKM2 overexpression (PKM2 vs PKM1), Co-IP of PKM2-STAT3, nuclear fractionation, VEGF/HIF1α pathway analysis, inducible PKM2 expression mouse models Cancer research Medium 34903602
2022 Dimeric/monomeric PKM2 nuclear translocation is promoted by ROS-induced oxidation at Cys423/Cys424, leading to glutathionylation of PKM2. Nuclear PKM2 then acts as a co-factor to promote HIF-1α-dependent gene induction, contributing to cardioprotective adaptive responses. Cys423/424 mutagenesis, glutathionylation assay, nuclear fractionation, HIF-1α reporter, cardiac-specific Pkm2 knockdown, ROS measurement, ischemia mouse model Acta pharmaceutica Sinica. B Medium 36815040
2024 PKM2 aggregates form in senescent cells and organs from aged mice, impairing PKM2 enzymatic activity and glycolytic flux, thereby driving cells into senescence. Small molecules capable of dissolving PKM2 aggregates alleviate senescence and extend lifespan in mouse models. PKM2 aggregate detection (biochemical fractionation, imaging), pyruvate kinase activity assay in senescent vs non-senescent cells, small molecule library screening, senescence marker analysis (SA-β-Gal, p16), lifespan measurement in aging mouse models Nature communications Medium 38982055
2021 PKM2 interacts with NF-κB and induces nuclear translocation of both PKM2 and NF-κB with assistance of importin 4. In the nucleus, PKM2-NF-κB complexes augment VEGFA transcription, promoting tumor angiogenesis. FBP promotes assembly of a FOXM1D-PKM2 heterooctamer that reduces PKM2 metabolic activity. Co-immunoprecipitation, nuclear fractionation, importin 4 knockdown, VEGFA promoter reporter, exosome-mediated VEGFA secretion assay, metabolic activity assay, tumor angiogenesis model Molecular oncology Medium 33314660
2022 CXCL12 signaling through CXCR4 and ACKR3 stimulates protein interactions among β-arrestin 2, PKM2, and ERK2, leading to dissociation of PKM2 from β-arrestin 2, reduced PKM2 oligomerization (tetramers to dimers/monomers), and increased glycolytic intermediates and pentose phosphate pathway metabolites. Luciferase protein complementation assays for protein-protein interactions, mass spectrometry of metabolites with isotopically labeled glucose, PKM2 oligomerization assay, tumor xenograft model Cells Medium 35681470
2021 PKM2 interacts with Oct4 in glioma stem cells, and this interaction is implicated in the regulation of glioma stemness. Silencing PKM2 enhances apoptosis and differentiation of glioma spheroids. DCA (a PDK inhibitor) increases PKM2/Oct4 complex formation and inhibits Oct4-dependent gene expression. Co-immunoprecipitation of PKM2-Oct4, PKM2 siRNA knockdown, apoptosis assays, differentiation markers, DCA treatment and Oct4 reporter Cell death & disease Medium 24481450
2021 PKM2 promotes IL-10 production via tetramerization-dependent ATP release and adenosine signaling, and PKM2 mediates autophagic activation by increasing phosphorylation of Beclin-1 in NPM1-mutated AML cells, contributing to cell survival. PKM2 knockdown, Beclin-1 phosphorylation assay, autophagy flux assay, cell viability assays International journal of biological sciences Low 30906218
2021 PKM2 regulates lipid homeostasis through an ER transmembrane protein TMEM33. Loss of PKM2 upregulates TMEM33, which recruits E3 ligase RNF5 to promote SCAP degradation. TMEM33 is transcriptionally regulated by NRF1, whose cleavage is controlled by PKM2 levels. Co-immunoprecipitation, SCAP degradation assay, NRF1 cleavage assay, TMEM33 promoter analysis, PKM2 global knockout mice (cholesterol measurement), allograft tumor model The EMBO journal Medium 34487377
2022 Vitamin B5 (pantothenate) is catabolized to coenzyme A (CoA) in a PANK-dependent manner, and CoA binds directly to PKM2, impeding its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation, and suppressing Th17 cell differentiation. PKM2-CoA binding assay, PKM2 phosphorylation assay, nuclear fractionation, STAT3 phosphorylation assay, Th17 differentiation assay, EAE and colitis mouse models Cell reports Medium 36450257
2024 Mannose directly binds PKM2, inhibiting its enzymatic activity and reducing lactate production, leading to decreased PKM2 lactylation and increased PKM2 acetylation, which causes nuclear translocation of PKM2 and NF-κB pathway activation, inducing NLRP1/Caspase-1/GSDMD/IL-1β-dependent pyroptosis in bladder cancer. Direct binding assay (mannose-PKM2), pyruvate kinase activity assay, lactate measurement, lactylation/acetylation assays on PKM2, nuclear fractionation, NF-κB pathway assay, pyroptosis markers, xenograft and organoid models Communications biology Medium 40312519

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 923 22056988
2012 PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 705 22901803
2016 PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nature communications 466 27779186
2016 PKM2, cancer metabolism, and the road ahead. EMBO reports 440 27856534
2020 Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis. Frontiers in oncology 396 32195169
2019 PKM2, function and expression and regulation. Cell & bioscience 396 31391918
2022 Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages. International journal of biological sciences 324 36439872
2012 Emerging roles of PKM2 in cell metabolism and cancer progression. Trends in endocrinology and metabolism: TEM 308 22824010
2014 PKM2 contributes to cancer metabolism. Cancer letters 281 24508027
2016 PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncology letters 248 26998110
2020 Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration. Circulation 242 32078387
2020 PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. The Journal of experimental medicine 238 32697823
2020 Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics. Cancer letters 206 33246091
2013 PKM2 regulates chromosome segregation and mitosis progression of tumor cells. Molecular cell 200 24316223
2022 FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2. Gut 197 35140065
2019 PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation. Protein & cell 194 30887444
2020 Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH. Redox biology 153 32863213
2022 PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke. Blood 135 34529778
2014 Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers. Oncotarget 133 24077665
2014 PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells. Nature communications 125 25412762
2014 The multifaceted regulation and functions of PKM2 in tumor progression. Biochimica et biophysica acta 122 25064846
2022 Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect. Military Medical Research 115 35596191
2022 ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth. Cancer research 107 34921016
2011 Regulation of glycolysis and gluconeogenesis by acetylation of PKM and PEPCK. Cold Spring Harbor symposia on quantitative biology 102 22096030
2023 Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence. Nature communications 99 36899022
2022 Myeloid Cell PKM2 Deletion Enhances Efferocytosis and Reduces Atherosclerosis. Circulation research 97 35400205
2015 Lack of Evidence for PKM2 Protein Kinase Activity. Molecular cell 94 26300261
2022 PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing. Circulation research 86 36200440
2018 PKM2, a potential target for regulating cancer. Gene 86 29775756
2012 Dual roles of PKM2 in cancer metabolism. Acta biochimica et biophysica Sinica 76 23212076
2014 Control of glioma cell death and differentiation by PKM2-Oct4 interaction. Cell death & disease 74 24481450
2018 Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect. Frontiers in cell and developmental biology 68 30087897
2022 GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. Redox biology 67 36116159
2020 PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment. Frontiers in immunology 66 33193421
2015 Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma. Oncotarget 66 25576919
2022 PKM2 Is Essential for Bladder Cancer Growth and Maintenance. Cancer research 57 34903602
2021 Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm. Frontiers in immunology 57 34759927
2021 Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment. Journal of Cancer 56 33995634
2021 FOXM1D potentiates PKM2-mediated tumor glycolysis and angiogenesis. Molecular oncology 53 33314660
2019 PKM2: A Potential Regulator of Rheumatoid Arthritis via Glycolytic and Non-Glycolytic Pathways. Frontiers in immunology 53 31921178
2024 LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM. Molecular cancer 51 38263157
2021 PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. The EMBO journal 50 34487377
2024 SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2. Cell reports. Medicine 49 39128469
2019 PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production. Scientific reports 49 31636306
2019 Glycolytic Enzyme PKM2 Mediates Autophagic Activation to Promote Cell Survival in NPM1-Mutated Leukemia. International journal of biological sciences 48 30906218
2024 Palmitic Acid Accelerates Endothelial Cell Injury and Cardiovascular Dysfunction via Palmitoylation of PKM2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 47 39665133
2017 PKM2 in carcinogenesis and oncotherapy. Oncotarget 46 29299177
2023 Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy. Circulation 40 37066795
2018 PKM2 and HIF-1α regulation in prostate cancer cell lines. PloS one 40 30216369
2025 Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine. Cell reports 39 39772395
2014 Activators of PKM2 in cancer metabolism. Future medicinal chemistry 39 25078136
2022 Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS. Acta pharmaceutica Sinica. B 38 36815040
2013 Does PKM(zeta) maintain memory? Brain research bulletin 38 24076105
2020 Modulation of PKM activity affects the differentiation of TH17 cells. Science signaling 37 33109748
2020 Upregulated PKM2 in Macrophages Exacerbates Experimental Arthritis via STAT1 Signaling. Journal of immunology (Baltimore, Md. : 1950) 36 32503893
2022 Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage. International journal of biological sciences 35 35280680
2024 METTL1 mediates PKM m7G modification to regulate CD155 expression and promote immune evasion in colorectal cancer. Journal of translational medicine 34 39741310
2022 Bile acids attenuate PKM2 pathway activation in proinflammatory microglia. Scientific reports 34 35087114
2022 Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation. Cell reports 33 36450257
2014 PKM2: the thread linking energy metabolism reprogramming with epigenetics in cancer. International journal of molecular sciences 33 24972138
2013 PKM and the maintenance of memory. F1000 biology reports 33 23413372
2025 SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch. Bone research 30 40087281
2022 Research progress on the role of PKM2 in the immune response. Frontiers in immunology 30 35967360
2018 Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2 Expression. Technology in cancer research & treatment 30 29343208
2025 PKM2-mediated metabolic reprogramming of microglia in neuroinflammation. Cell death discovery 27 40189596
2024 The role of PKM2 in cancer progression and its structural and biological basis. Journal of physiology and biochemistry 27 38329688
2024 PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer. The EMBO journal 27 38750259
2023 The interaction between apigenin and PKM2 restrains progression of colorectal cancer. The Journal of nutritional biochemistry 25 37597817
2021 Parthenolide Derivatives as PKM2 Activators Showing Potential in Colorectal Cancer. Journal of medicinal chemistry 25 34847663
2018 miR-625-5p/PKM2 negatively regulates melanoma glycolysis state. Journal of cellular biochemistry 25 30500994
2018 PKM2 promotes reductive glutamine metabolism. Cancer biology & medicine 24 30891326
2022 Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases. Journal of cardiovascular translational research 23 36178660
2024 LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity. Cancer letters 22 38218456
2024 PKM2 aggregation drives metabolism reprograming during aging process. Nature communications 20 38982055
2024 PTBP1 crotonylation promotes colorectal cancer progression through alternative splicing-mediated upregulation of the PKM2 gene. Journal of translational medicine 20 39497094
2023 Glycolytic enzyme PKM2 regulates cell senescence but not inflammation in the process of osteoarthritis. Acta biochimica et biophysica Sinica 20 37525533
2022 JOSD2 regulates PKM2 nuclear translocation and reduces acute myeloid leukemia progression. Experimental hematology & oncology 20 35836282
2021 A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme. Metabolic brain disease 20 33651273
2025 March2 Alleviates Aortic Aneurysm/Dissection by Regulating PKM2 Polymerization. Circulation research 19 40079144
2023 Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling. Nucleic acids research 19 37224531
2023 The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases. Molecular neurobiology 19 38157121
2021 Extracellular PKM2 facilitates organ-tissue fibrosis progression. iScience 19 34693222
2024 LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39342418
2022 PKM2 Modulation in Head and Neck Squamous Cell Carcinoma. International journal of molecular sciences 18 35054968
2024 PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation. Journal of virology 17 38319105
2024 Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role. Molecular cell 17 39153475
2023 Simultaneous suppression of PKM2 and PHGDH elicits synergistic anti-cancer effect in NSCLC. Frontiers in pharmacology 17 37284309
2025 PKM2 controls cochlear development through lactate-dependent transcriptional regulation. Proceedings of the National Academy of Sciences of the United States of America 16 39773029
2025 Mannose inhibits PKM2 lactylation to induce pyroptosis in bladder cancer and activate antitumor immune responses. Communications biology 16 40312519
2025 Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator. Journal of biomedical science 16 40790192
2022 The CXCL12/CXCR4/ACKR3 Signaling Axis Regulates PKM2 and Glycolysis. Cells 16 35681470
2021 Dual Covalent Inhibition of PKM and IMPDH Targets Metabolism in Cutaneous Metastatic Melanoma. Cancer research 16 34099492
2025 SGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2. Cellular and molecular life sciences : CMLS 15 40237854
2024 N6-methyladenosine-modified SRPK1 promotes aerobic glycolysis of lung adenocarcinoma via PKM splicing. Cellular & molecular biology letters 15 39095708
2020 Regulation of trophoblast cell invasion by Pyruvate Kinase isozyme M2 (PKM2). Placenta 15 33070034
2024 Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications. Current medicinal chemistry 14 37455458
2024 Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis. International immunopharmacology 14 38359663
2023 Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review. Medicine 14 37861491
2021 Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers. Cancers 14 33478099
2022 Linc-UROD stabilizes ENO1 and PKM to strengthen glycolysis, proliferation and migration of pancreatic cancer cells. Translational oncology 13 36413861

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