Affinage

PIM3

Serine/threonine-protein kinase pim-3 · UniProt Q86V86

Length
326 aa
Mass
35.9 kDa
Annotated
2026-06-10
83 papers in source corpus 36 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIM3 is a constitutively active serine/threonine kinase that functions broadly as a pro-survival, pro-proliferative, and pro-migratory effector across cancer, vascular, endocrine, and stem-cell contexts (PMID:16818649, PMID:24789328). Its best-characterized substrate is the pro-apoptotic protein BAD, which PIM3 phosphorylates specifically at Ser112 (not Ser136) to inactivate it and suppress apoptosis—an activity replicated across pancreatic, colon, hepatoma, and leukemic cells (PMID:16818649, PMID:17270021, PMID:32764981). Beyond BAD, PIM3 phosphorylates a defined substrate set that explains its diverse phenotypes: MAPK1/ERK2 at T185/Y187 to drive proliferation (PMID:38128397), CXCR4 at Ser339 to promote migration and metastatic colonization (PMID:32764981, PMID:36315303), the KSHV antigen LANA at Ser205/206 to enable viral reactivation (PMID:19266083), and MLF2 at Ser65 to stabilize it via USP21-mediated protection from STUB1 ubiquitination (PMID:41090348). Its kinase activity is required for these outputs, as kinase-dead mutants (e.g., K69M) abolish BAD phosphorylation, proliferation, and tumor-promoting vasculogenesis (PMID:12748291, PMID:24789328). PIM3 expression is transcriptionally driven by multiple oncogenic inputs—EWS/ETS fusions (PMID:12748291), Ets-1 (PMID:19154409), c-Myc (PMID:21646687), Tax/NF-κB (PMID:28833639), and YY1 (PMID:39850120)—and is post-translationally stabilized by TCTP, which binds PIM3's C-terminus to block its ubiquitin-proteasomal degradation (PMID:24165482); conversely, mTORC1 represses PIM3 via SREBP-encoded miR-33 (PMID:29167471, PMID:29170467). In normal physiology, PIM3 negatively regulates glucose-stimulated insulin secretion in β-cells by suppressing ERK1/2 through SOCS6 (PMID:21099329), protects the endothelial vascular barrier by maintaining junctional cadherin-5 and catenins (PMID:39627185), and represses the totipotent 2-cell-like state in embryonic stem cells via an AMPK–HDAC4/5 axis that silences MuERVL elements (PMID:36150380). As an oncogene PIM3 acts as a tumor promoter rather than initiator, accelerating hepatocyte cell cycle progression without inducing spontaneous tumors (PMID:20101231).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established PIM3 as an oncogenic effector downstream of a fusion oncoprotein, answering whether its kinase activity is functionally required for transformation.

    Evidence Microarray, forced expression, kinase-dead co-expression, and in vivo tumorigenesis in immunodeficient mice for EWS/ETS-driven Ewing sarcoma

    PMID:12748291

    Open questions at the time
    • Did not identify direct phosphorylation substrates
    • Mechanism of anchorage-independent growth not resolved at the molecular level
  2. 2006 High

    Identified BAD Ser112 as a direct PIM3 phosphorylation target, defining the molecular basis of its anti-apoptotic activity.

    Evidence shRNA knockdown and phospho-specific Western blot in pancreatic cancer cells; replicated in colon cancer (2007)

    PMID:16818649 PMID:17270021

    Open questions at the time
    • Site specificity (Ser112 vs Ser136) shown by KD but not by in vitro kinase assay in original work
    • Other pro-survival substrates not yet mapped
  3. 2009 Medium

    Extended PIM3 substrate range beyond cancer to a viral target, showing it phosphorylates KSHV LANA at Ser205/206 to drive lytic reactivation.

    Evidence Pim kinase overexpression, phosphosite identification, and reactivation assays in naturally infected cells

    PMID:19266083

    Open questions at the time
    • Redundancy with PIM1 not fully separated
    • Physiological PIM3 levels during natural reactivation not established
  4. 2010 High

    Distinguished PIM3 as a tumor promoter rather than an initiator, clarifying its causal role in hepatocarcinogenesis.

    Evidence Liver-specific transgenic mice with DEN-induced HCC and proliferation/vascular readouts

    PMID:20101231

    Open questions at the time
    • Direct substrate driving accelerated cell cycle in vivo not identified
    • No spontaneous tumor model
  5. 2009 Medium

    Defined a non-cancer cellular role: PIM3 localizes to lamellipodia in an actin-dependent manner and is required for endothelial migration and tube formation.

    Evidence Immunofluorescence, cytochalasin D treatment, FAK co-localization, and siRNA functional assays in endothelial cells

    PMID:19229879

    Open questions at the time
    • No cytoskeletal substrate identified at this stage
    • Mechanism linking localization to migration unresolved
  6. 2013 High

    Revealed how PIM3 protein levels are controlled, identifying TCTP as a stabilizer that blocks proteasomal degradation.

    Evidence Yeast two-hybrid, Co-IP, domain mapping, proteasome inhibitor experiments, and in vivo tumor growth

    PMID:24165482

    Open questions at the time
    • E3 ligase mediating PIM3 ubiquitination not identified
    • Mechanism by which TCTP shields PIM3 unknown
  7. 2011 Medium

    Placed PIM3 within the c-Myc transcriptional program, identifying it as a direct Myc target and a vulnerability in Myc-driven lymphoma.

    Evidence ChIP for c-Myc at PIM3 E-boxes, pan-PIM inhibition, and cell death assays in Myc-transgenic/Burkitt models

    PMID:21646687

    Open questions at the time
    • Caspase-independent death mechanism not defined
    • PIM3-specific (vs pan-PIM) contribution not isolated
  8. 2011 High

    Uncovered a normal endocrine function: PIM3 restrains glucose-stimulated insulin secretion via SOCS6-mediated ERK1/2 suppression.

    Evidence Pim3 knockout mice, GSIS assays, glucose tolerance tests, Co-IP for SOCS6, and SOCS6 overexpression epistasis

    PMID:21099329

    Open questions at the time
    • Direct phosphorylation target linking PIM3 to SOCS6 not shown
    • Compensation by other PIM family members not excluded
  9. 2014 High

    Established kinase-dependence of PIM3's pro-angiogenic and proliferative output using a kinase-dead K69M mutant.

    Evidence Wild-type vs K69M overexpression, shRNA, xenograft, and angiogenic factor profiling in pancreatic cancer

    PMID:24789328

    Open questions at the time
    • Whether STAT3/Survivin/VEGF effects are direct substrates or downstream consequences unresolved
  10. 2015 Medium

    Identified post-transcriptional repression of PIM3 by miR-33a and linked PIM3 to AKT/GSK-3β/β-catenin signaling and chemoresistance.

    Evidence Dual luciferase reporter, pathway Western blots, and in vivo chemosensitivity assays in pancreatic cancer

    PMID:25971209

    Open questions at the time
    • Direct PIM3 substrate in the AKT/GSK-3β axis not identified
    • Single regulatory miRNA tested
  11. 2017 Medium

    Connected PIM3 regulation to nutrient/growth signaling, showing mTORC1 suppresses PIM3 via SREBP and miR-33.

    Evidence Rapamycin treatment, TSC knockout cells, SREBP manipulation, and in vivo mouse liver feeding

    PMID:29167471 PMID:29170467

    Open questions at the time
    • Functional consequence of PIM3 induction under mTORC1 inhibition not fully characterized
    • Single lab
  12. 2017 Medium

    Demonstrated PIM3 supports cancer stemness through STAT3 activation in pancreatic cancer.

    Evidence siRNA knockdown, STAT3 activity assays, CD24+ESA+ flow cytometry, and STAT3 rescue

    PMID:28775772

    Open questions at the time
    • Whether STAT3 phosphorylation is direct or indirect not established
  13. 2018 Medium

    Extended PIM3's migratory role to melanoma metastasis via STAT3-driven EMT.

    Evidence shRNA, migration/invasion assays, in vivo metastasis model, and EMT marker Western blots

    PMID:29370558

    Open questions at the time
    • Direct STAT3 phosphorylation by PIM3 not demonstrated by kinase assay
  14. 2020 Medium

    Used phosphoproteomics to broaden the PIM3 signaling map and identify RhoA activation driving cytoskeletal rearrangement and migration.

    Evidence Quantitative phosphoproteomics, RhoA activity assay, and cytoskeletal analysis in liver cancer cells

    PMID:31994402

    Open questions at the time
    • Direct Rho-modulator substrates inferred from phosphoproteomics not individually validated
  15. 2020 Medium

    Identified CXCR4 Ser339 as a PIM3 phosphorylation target promoting AML migration.

    Evidence Co-IP of PIM3 with pCXCR4(Ser339), migration assay, and pBAD(Ser112) Western blot

    PMID:32764981

    Open questions at the time
    • Direct in vitro kinase assay on CXCR4 not shown
    • Single cancer type
  16. 2022 High

    Validated the PIM3-CXCR4 axis as a driver of metastasis using genetic and pharmacological loss-of-function.

    Evidence CRISPR/Cas9 knockout, overexpression, AMD3100 CXCR4 blockade, and tail-vein metastasis in hepatoblastoma

    PMID:36315303

    Open questions at the time
    • Whether surface CXCR4 increase is solely phosphorylation-driven not isolated
  17. 2022 Medium

    Revealed a developmental role: PIM3 represses the totipotent 2-cell-like state via an AMPK-HDAC4/5-MuERVL chromatin axis.

    Evidence PIM3 knockout ESCs, AMPK phosphorylation, HDAC4/5 fractionation, and chromatin modification analysis at MuERVL loci

    PMID:36150380

    Open questions at the time
    • Direct PIM3 substrate upstream of AMPK not identified
    • Single lab
  18. 2023 Medium

    Identified MAPK1/ERK2 (T185/Y187) as a direct PIM3 substrate driving proliferation, and a small-molecule inhibitor (corynoline).

    Evidence Pull-down, CETSA, in vitro kinase assay, and patient-derived xenograft in esophageal carcinoma

    PMID:38128397

    Open questions at the time
    • Dual-residue (T/Y) phosphorylation mechanism by a Ser/Thr kinase not mechanistically explained
    • Single lab
  19. 2024 High

    Established a protective vascular function distinct from its oncogenic roles: endothelial PIM3 maintains junctional integrity to limit metastatic colonization.

    Evidence scRNA-seq of lung endothelial cells, pharmacological PIM inhibition, permeability assays, and multiple metastasis models

    PMID:39627185

    Open questions at the time
    • Direct junctional-protein substrate not identified
    • PIM3-specific vs pan-PIM contribution not separated pharmacologically
  20. 2025 High

    Defined a stabilization mechanism whereby PIM3 phosphorylates MLF2 at Ser65 to recruit USP21 and protect it from STUB1-mediated degradation, driving osteosarcoma metastasis.

    Evidence In vivo CRISPR activation screen, phosphosite mapping, ubiquitination assays, Co-IP, and xenograft metastasis

    PMID:41090348

    Open questions at the time
    • Generality of phospho-stabilization mechanism to other substrates unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIM3 achieves overlapping but context-specific substrate selection, and whether its protective (endothelial barrier, β-cell) versus oncogenic functions reflect distinct substrate pools, complexes, or localizations, remains unresolved.
  • No structural basis for substrate selectivity established for PIM3 itself
  • Functional redundancy with PIM1/PIM2 incompletely mapped
  • Most disease-context substrates inferred without in vitro kinase validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 2
Partners
AKTBADCXCR4MAPK1MLF2SOCS6TCTPUSP21

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 PIM3 serine/threonine kinase phosphorylates the pro-apoptotic protein BAD at Ser112 (but not Ser136) in human pancreatic cancer cells, inactivating BAD and preventing apoptosis; PIM3 knockdown reduced pBAD(Ser112) and Bcl-XL expression and promoted apoptosis. shRNA knockdown, Western blot for pBAD(Ser112) and pBAD(Ser136), flow cytometry for apoptosis Cancer Research High 16818649
2007 PIM3 phosphorylates BAD at Ser112 in human colon cancer cells, inactivating BAD to prevent apoptosis; PIM3 knockdown specifically abrogated Ser112 phosphorylation and promoted apoptosis. shRNA knockdown, Western blot, co-localization by immunohistochemistry Cancer Science High 17270021
2005 PIM3 is aberrantly expressed in human hepatocellular carcinoma cell lines but not normal liver; RNA interference-mediated ablation of PIM3 attenuated cell proliferation and enhanced apoptosis in hepatoma cell lines. RNA interference, cell proliferation assay, apoptosis assay; fluorescent differential display to identify gene International Journal of Cancer Medium 15540201
2003 PIM3 is a direct transcriptional target of EWS/ETS oncoproteins; forced expression of PIM3 promotes anchorage-independent growth, and co-expression of a kinase-deficient PIM3 mutant attenuated EWS/FLI1-mediated tumorigenesis in immunodeficient mice. Microarray expression analysis, forced expression assay, kinase-dead mutant co-expression, in vivo tumorigenesis assay Molecular and Cellular Biology High 12748291
2008 The transcription factor Ets-1 binds the PIM3 promoter (between -249 and -183 bp) and drives constitutive PIM3 expression in human pancreatic cancer cells; mutation of the Ets-1 binding site (-216 to -211 bp) reduced promoter activity, and dominant-negative Ets-1 or Ets-1 siRNA reduced PIM3 expression, pBAD(Ser112) levels, and induced apoptosis—effects reversed by PIM3 cDNA re-introduction. Luciferase reporter with deletion mutants, chromatin immunoprecipitation (ChIP), dominant-negative transfection, Ets-1 siRNA, rescue experiment with PIM3 cDNA Cancer Science High 19154409
2009 PIM3 (along with PIM1) phosphorylates the KSHV latency-associated nuclear antigen LANA on serine residues 205 and 206, counteracting LANA-mediated repression of lytic gene transcription and thereby promoting KSHV reactivation from latency. Overexpression of Pim kinases, identification of phosphorylation sites on LANA, KSHV reactivation assays in naturally infected cells PLoS Pathogens Medium 19266083
2007 PIM3 expression in mouse embryonic stem cells is upregulated by LIF/gp130/STAT3 signaling; overexpression of PIM3 enhanced ES cell self-renewal and resistance to LIF withdrawal, while knockdown increased spontaneous differentiation and apoptosis. Granulocyte colony-stimulating factor:gp130 chimeric receptor + hormone-dependent STAT3-ER system, clonal self-renewal assay, shRNA knockdown Stem Cells Medium 17717068
2010 PIM3 liver-specific transgenic mice do not develop spontaneous HCC but show accelerated hepatocyte cell cycle progression; upon diethylnitrosamine (DEN) treatment, these mice develop HCC with higher incidence (80% vs 40%) and heavier tumor burden, demonstrating PIM3 acts as a tumor promoter rather than initiator. Liver-specific transgenic mouse model, DEN-induced hepatocarcinogenesis, histological analysis, immunohistochemistry for proliferating cells and CD31+ vascular areas Oncogene High 20101231
2009 PIM3 is expressed at high levels in endothelial cells where it localizes to lamellipodia and co-localizes with focal adhesion kinase (FAK); treatment with the actin polymerization inhibitor cytochalasin D dispersed PIM3 from lamellipodia; siRNA-mediated PIM3 knockdown impaired EC spreading, migration, proliferation, and tube-like structure formation in Matrigel assay. Immunofluorescence localization, co-localization with FAK, cytochalasin D treatment, siRNA knockdown, Matrigel tube formation assay Journal of Cellular Physiology Medium 19229879
2013 Translationally controlled tumor protein (TCTP) interacts with PIM3 through PIM3's C-terminal region and TCTP's N-terminal region; TCTP overexpression increases PIM3 protein levels dose-dependently, while TCTP knockdown reduces PIM3 protein (but not mRNA) via the ubiquitin-proteasome degradation system, establishing TCTP as a regulator of PIM3 protein stability. Yeast two-hybrid screen, co-immunoprecipitation, domain mapping, RNAi-mediated knockdown, proteasome inhibitor experiments, in vitro and in vivo tumor growth assays Molecular Cancer Research High 24165482
2011 PIM3 is a direct transcriptional target of c-Myc, which binds to conserved E-boxes in the PIM3 gene; lymphomas in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated PIM3 levels; pan-PIM kinase inhibition in Myc-induced lymphoma causes caspase-independent cell death. Chromatin immunoprecipitation (ChIP) for c-Myc binding to PIM3 E-boxes, pharmacological Pim kinase inhibitor, cell death assay Oncotarget Medium 21646687
2010 PIM3 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells; Pim3-/- mice show enhanced second-phase insulin secretion, increased glucose tolerance, and increased insulin sensitivity; PIM3 physically interacts with SOCS6, whose levels are reduced in Pim3-/- islets; overexpression of SOCS6 inhibits glucose-induced ERK1/2 activation, suggesting PIM3 suppresses insulin secretion by inhibiting ERK1/2 through SOCS6. Pim3 knockout mouse, glucose-stimulated insulin secretion assay in MIN6 cells and isolated islets, in vivo glucose tolerance test, ERK1/2 phosphorylation assay, co-immunoprecipitation for SOCS6, SOCS6 overexpression Islets High 21099329
2014 PIM3 kinase activity promotes pancreatic cancer vasculogenesis and tumor growth; wild-type PIM3 overexpression increased Bad(Ser112) phosphorylation and proliferation, while kinase-dead PIM3 (K69M mutant) reduced these effects; PIM3 upregulated pSTAT3(Tyr705), pSurvivin(Thr34), and angiogenic factors including VEGF, HGF, EGF, and FGF-2 in a kinase-dependent manner. Stable overexpression of wild-type vs. kinase-dead K69M-PIM3 mutant, shRNA knockdown, xenograft mouse model, Western blot, histological analysis of CD31+ vascular areas Oncology Reports High 24789328
2015 miR-33a directly targets the 3'-UTR of PIM3 mRNA to suppress its expression in pancreatic cancer; PIM3 suppression by miR-33a leads to downregulation of the AKT/GSK-3β/β-catenin pathway, inhibiting tumor growth and increasing gemcitabine chemosensitivity. Dual luciferase reporter assay for miR-33a targeting PIM3 3'-UTR, Western blot for downstream signaling, in vitro and in vivo proliferation/chemosensitivity assays Oncotarget Medium 25971209
2017 mTORC1 suppresses PIM3 expression via SREBP transcription factors and miR-33 (an intronic microRNA encoded within the SREBP loci); rapamycin inhibition of mTORC1 induces PIM3 transcript and protein levels; this pathway operates in cells with TSC loss-of-function and in mouse liver upon feeding. Rapamycin treatment, TSC knockout cells, SREBP manipulation, miR-33 expression analysis, in vivo mouse liver feeding experiments Scientific Reports Medium 29167471 29170467
2018 PIM3 promotes melanoma cell migration and invasion by promoting STAT3 phosphorylation, which induces expression of EMT-related transcription factors Slug, Snail, and ZEB1; PIM3 knockdown inhibited B16F10 cell migration in vitro and reduced pulmonary metastasis in a tumor-bearing mouse model. shRNA knockdown, in vitro migration/invasion assay, in vivo metastasis mouse model, Western blot for STAT3 phosphorylation and EMT markers Cancer Biology & Therapy Medium 29370558
2016 PIM3 contributes to radioresistance in pancreatic cancer cells by attenuating G2/M phase cell cycle arrest and DNA damage response; PIM3 silencing elevated phosphorylation of histone H2AX (γH2AX, a DNA double-strand break marker) and decreased ATM kinase activation, enhancing radiosensitivity in vitro and in vivo. Stable PIM3 overexpression and shRNA knockdown, γH2AX and ATM phosphorylation by Western blot, cell cycle analysis, xenograft in vivo radiosensitivity assay Biochemical and Biophysical Research Communications Medium 27016481
2009 PIM3 expression in cardiomyocytes is upregulated by anoxic preconditioning via a p38 MAPK signaling pathway; transfection of PIM3 into rat cardiomyocytes attenuated anoxia/reoxygenation injury; inhibition of p38 MAPK by SB203580 abolished both PIM3 upregulation and the cardioprotective effect. PIM3 expression vector transfection into rat cardiomyocytes, p38 MAPK inhibitor (SB203580), anoxia/reoxygenation model, cell viability and apoptosis assays International Journal of Biochemistry & Cell Biology Medium 19505587
2020 PIM3 overexpression promotes liver cancer cell migration by activating RhoA GTPase through phosphorylation of multiple Rho GTPase modulators, leading to cytoskeletal rearrangements; quantitative phosphoproteomics revealed PIM3-induced phosphorylation changes across signal transduction, cell cycle, and apoptosis networks. Quantitative proteomics and phosphoproteomics in PIM3-overexpressing liver cancer cells, RhoA activity assay, cytoskeletal analysis Journal of Proteome Research Medium 31994402
2020 PIM3 overexpression promotes AML cell migration via CXCR4; PIM3-overexpressing AML cells exhibited increased CXCR4 phosphorylation at Ser339, and phosphorylated CXCR4 physically interacted with PIM3 by co-immunoprecipitation; PIM3 also phosphorylated BAD at Ser112 to protect against apoptosis. Co-immunoprecipitation of PIM3 and pCXCR4(Ser339), cell migration assay, Western blot for pBAD(Ser112), flow cytometry OncoTargets and Therapy Medium 32764981
2022 PIM3 suppresses the totipotent 2-cell-like state in embryonic stem cells via an AMPK-HDAC4/5 axis; loss of PIM3 increases AMPK phosphorylation, causing HDAC4/5 nuclear export, which reduces H3K9me1/2 and increases H3K9ac on MuERVL retroviral elements, thereby activating 2-cell genes. PIM3 knockout ESCs, AMPK phosphorylation assays, HDAC4/5 nuclear/cytoplasmic fractionation, chromatin modification (H3K9ac, H3K9me1/2) analysis at MuERVL loci, pharmacological PIM3 inhibition Stem Cell Reports Medium 36150380
2017 In adult T-cell leukemia, viral Tax protein induces PIM3 expression through NF-κB signaling; PIM3 knockdown inhibited growth of HTLV-1-infected T cells; PIM1/3 kinase inhibitor NJC97-NH induced G2/M arrest with downregulation of cyclin A and cyclin B1, and apoptosis with downregulation of XIAP and Mcl-1 via inhibition of NF-κB (decreased IκBα and RelA phosphorylation). siRNA knockdown of PIM3 and RelA, pharmacological Pim inhibitor, EMSA for NF-κB DNA binding, Western blot, cell cycle and apoptosis analysis European Journal of Haematology Medium 28833639
2017 PIM3 maintains stemness of pancreatic cancer cells by activating the STAT3 signaling pathway; PIM3 silencing decreased proportions of CD24+ESA+ cancer stem-like cells and reduced stemness-associated transcription factors including STAT3 phosphorylation; restoration of STAT3 activity rescued the stem cell-like phenotype in PIM3-silenced cells. PIM3 siRNA knockdown, STAT3 phosphorylation/transcriptional activity assay, CD24+ESA+ cell population flow cytometry, STAT3 rescue experiment Journal of Cancer Medium 28775772
2019 Aldosterone stimulates PIM3 expression in the distal nephron in vitro (mCCDcl1 cells), ex vivo (mouse kidney slices), and in vivo; Pim3-/- mice display upregulated RAAS (elevated aldosterone and plasma renin activity) but no overt salt-losing phenotype, potentially compensated by upregulation of PIM1 and PIM2 in the kidney. Germline Pim3 knockout mouse, aldosterone treatment in multiple systems, electrolyte/blood pressure measurements, expression analysis of PIM family members and Na+ transporters Physiological Reports Medium 31397090
2022 PIM3 kinase promotes hepatoblastoma metastasis by upregulating phosphorylation and cell surface expression of CXCR4; PIM3 knockout by CRISPR/Cas9 impaired lung metastasis formation in vivo; CXCR4 blockade with AMD3100 decreased the metastatic phenotype of PIM3-overexpressing cells. CRISPR/Cas9 PIM3 knockout, stable PIM3 overexpression, tail vein injection metastasis model, AMD3100 CXCR4 blockade, CXCR4 surface expression analysis Clinical & Experimental Metastasis High 36315303
2021 CRISPR/Cas9-mediated PIM3 knockout in hepatoblastoma cells decreased proliferation, viability, motility, tumor growth in xenograft model, and cancer cell stemness (tumorsphere formation, CD133 expression, stemness marker mRNAs); reintroduction of PIM3 rescued the malignant phenotype. CRISPR/Cas9 dual gRNA knockout, xenograft murine model, RNA sequencing, tumorsphere assay, CD133 flow cytometry, PIM3 rescue experiment Cancer Gene Therapy High 33864024
2025 PIM3-mediated phosphorylation of myeloid leukemia factor 2 (MLF2) at Ser65 enhances MLF2 stability by promoting its interaction with the deubiquitinase USP21, thereby protecting MLF2 from STUB1-mediated ubiquitination and proteasomal degradation at Lys119; MLF2 promotes osteosarcoma metastasis by disrupting the BiP-IRE1α interaction, activating the IRE1α/XBP1-S-MMP9 axis. In vivo CRISPR activation screen combined with STUB1 interactome, phosphorylation site mapping, ubiquitination assays, Co-IP for USP21/MLF2/PIM3 interactions, xenograft metastasis model Journal of Clinical Investigation High 41090348
2024 PIM3 inhibition increases vascular leakage and metastatic colonization in the lung; endothelial PIM3 (activated by JAK-STAT) protects the vascular barrier by maintaining junctional cadherin-5 and catenins α, β, and δ at endothelial cell junctions; PIM inhibition impairs the EC barrier. scRNA-seq of lung ECs in metastasis models, pharmacological PIM inhibition, vascular permeability assay, junctional protein expression analysis, spontaneous metastasis mouse models Nature Communications High 39627185
2025 PIM3 physically interacts with and activates the Akt signaling pathway in nucleus pulposus cells to regulate downstream mTOR and FoxO1, modulating cell viability and senescence in a kinase-activity-dependent manner; AAV-mediated PIM3 overexpression in an IDD rat model improved ECM integrity and reduced senescence. Co-immunoprecipitation of PIM3 and Akt, knockdown and overexpression including kinase-dead mutant, Akt/mTOR/FoxO1 phosphorylation assays, AAV in vivo model Translational Research Medium 41478528
2023 PIM3 phosphorylates MAPK1 (ERK2) at T185 and Y187 in esophageal squamous cell carcinoma cells, promoting cell proliferation and tumor development; corynoline directly binds PIM3 and inhibits its kinase activity; PIM3 deletion induced apoptosis with upregulated cleaved caspase-9 and reduced BAD phosphorylation at S112. Pull-down assay, cellular thermal shift assay (CETSA), kinase assay, Western blot for pMAPK1(T185/Y187) and pBAD(S112), patient-derived xenograft model Phytomedicine Medium 38128397
2025 PIM3 is upregulated by the transcription factor YY1, which translocates from the cytoplasm to the nucleus under hyperglycemia and binds the PIM3 promoter, enhancing PIM3 transcriptional activity; PIM3 or YY1 knockdown reduced cardiac hypertrophy markers and attenuated diabetic cardiac dysfunction in mice. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay for YY1-PIM3 promoter interaction, siRNA and lentivirus-mediated knockdown, streptozotocin diabetic mouse model, echocardiography Iranian Journal of Basic Medical Sciences Medium 39850120
2025 The compound CSH-4044 (isolated from fermented wheat germ extract) is an ATP-competitive inhibitor of PIM kinases including PIM3; it suppresses PIM3-driven BAD phosphorylation in pancreatic cancer cells; co-crystal structure of CSH-4044 with PIM1 revealed critical hydrophobic and hydrogen-bonding interactions at the ATP binding site. X-ray co-crystallography of PIM1-CSH-4044, kinase profiling, BAD phosphorylation assay in pancreatic cancer cells bioRxivpreprint Medium bio_10.1101_2025.10.22.683941
2019 Knockdown of PIM3 inhibits ferroptosis in myocardial I/R injury, alleviating myocardial damage; PIM3 expression is increased by myocardial I/R or OGD/R, and PIM3 silencing reduced ROS, MDA, and iron content while increasing SOD, GPX4, and FTH1. In vivo rat myocardial I/R model, H9c2 OGD/R cell model, siRNA knockdown, Western blot for ferroptosis markers (TfR1, FTH1, GPX4), ROS/MDA/SOD assays Genes & Genomics Low 38148455
2025 ETS1 transcription factor promotes PIM3 expression under OGD/R conditions (simulating myocardial ischemia-reperfusion injury) by binding the PIM3 promoter; ETS1 knockdown suppressed ferroptosis and myocardial injury through reducing PIM3 expression; the ETS1→PIM3 axis exacerbates ferroptosis in cardiomyocytes. OGD/R H9C2 cell model, mouse MIRI model, ETS1 knockdown, Western blot for ETS1/PIM3/ferroptosis markers (GPX4, SLC7A11, FTH1), immunofluorescence Experimental Cell Research Low 40189183
2019 Cholesterol promotes CRC cell proliferation partly through the miR-33a/PIM3 axis; PIM3 was identified as a direct target of miR-33a by dual luciferase reporter assay; PIM3 modulates CRC cell proliferation and apoptosis by phosphorylating p27, p21, and BAD. Dual luciferase reporter assay, Western blot for pBad/pp27/pp21, CCK-8 and flow cytometry with cholesterol treatment and miR-33a manipulation Biochemical and Biophysical Research Communications Low 30827510

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. Cancer research 157 16818649
2007 Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis. Cancer science 110 17270021
2005 Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines. International journal of cancer 87 15540201
2012 Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorganic & medicinal chemistry letters 83 22727640
2011 Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer science 75 21518143
2003 PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Molecular and cellular biology 68 12748291
2007 Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression. Journal of cancer research and clinical oncology 66 17876606
2015 MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine. Oncotarget 64 25971209
2009 KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS pathogens 60 19266083
2007 Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases Pim-1 and Pim-3. Stem cells (Dayton, Ohio) 58 17717068
2010 Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in the liver. Oncogene 56 20101231
2019 Cholesterol regulates cell proliferation and apoptosis of colorectal cancer by modulating miR-33a-PIM3 pathway. Biochemical and biophysical research communications 45 30827510
2013 A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression. Molecular cancer research : MCR 42 24165482
2011 The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas. Oncotarget 41 21646687
2016 MiR-377 inhibits the proliferation of pancreatic cancer by targeting Pim-3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 27638830
2011 Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorganic & medicinal chemistry letters 40 21945284
2008 Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells. Cancer science 36 19154409
2014 Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression. World journal of gastroenterology 34 25071334
2009 Pim-3 is expressed in endothelial cells and promotes vascular tube formation. Journal of cellular physiology 31 19229879
2013 Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine. Cancer biology & therapy 30 23760491
2009 Pim-3 protects against cardiomyocyte apoptosis in anoxia/reoxygenation injury via p38-mediated signal pathway. The international journal of biochemistry & cell biology 27 19505587
2018 Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation. Cancer biology & therapy 26 29370558
2017 Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells. Oncotarget 26 29069816
2016 Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells. Biochemical and biophysical research communications 22 27016481
2014 Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis. Oncology reports 21 24789328
2015 MicroRNA‑506 participates in pancreatic cancer pathogenesis by targeting PIM3. Molecular medicine reports 20 26238203
2019 Bufothionine exerts anti-cancer activities in gastric cancer through Pim3. Life sciences 19 31260686
2019 AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK. International journal of molecular sciences 18 30654529
2015 Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells. Asian Pacific journal of cancer prevention : APJCP 18 25921139
2014 Differential expression of Pim-3, c-Myc, and p-p27 proteins in adenocarcinomas of the gastric cardia and distal stomach. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 24488669
2010 Pim3 negatively regulates glucose-stimulated insulin secretion. Islets 17 21099329
2009 Pim-3 protects against hepatic failure in D-galactosamine (D-GalN)-sensitized rats. European journal of clinical investigation 17 20039932
2017 Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients. Scientific reports 16 29167471
2021 CRISPR/Cas9-mediated knockout of PIM3 suppresses tumorigenesis and cancer cell stemness in human hepatoblastoma cells. Cancer gene therapy 15 33864024
2013 Pim-3 promotes the growth of human pancreatic cancer in the orthotopic nude mouse model through vascular endothelium growth factor. The Journal of surgical research 15 23845873
2005 Association of the PIM3 allele of the alpha-1-antitrypsin gene with chronic obstructive pulmonary disease. Clinical biochemistry 15 15820782
2024 PIM3 Kinase: A Promising Novel Target in Solid Cancers. Cancers 13 38339286
2020 Proto-Oncogene Serine/Threonine Kinase PIM3 Promotes Cell Migration via Modulating Rho GTPase Signaling. Journal of proteome research 13 31994402
2020 PIM3 Promotes the Proliferation and Migration of Acute Myeloid Leukemia Cells. OncoTargets and therapy 13 32764981
2015 Knockdown of Pim-3 suppresses the tumorigenicity of glioblastoma by regulating cell cycle and apoptosis. Cellular and molecular biology (Noisy-le-Grand, France) 13 25817345
2019 The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival. Journal of pediatric surgery 11 30898394
2009 [Effect of ginsenoside Rg3 on Pim-3 and Bad proteins in human pancreatic cancer cell line PANC-1]. Ai zheng = Aizheng = Chinese journal of cancer 11 19624871
2022 PIM3-AMPK-HDAC4/5 axis restricts MuERVL-marked 2-cell-like state in embryonic stem cells. Stem cell reports 10 36150380
2018 PIM3 Functions as Oncogenic Factor and Promotes the Tumor Growth and Metastasis in Colorectal Cancer. Anatomical record (Hoboken, N.J. : 2007) 10 30417983
2017 Pim-3 Regulates Stemness of Pancreatic Cancer Cells via Activating STAT3 Signaling Pathway. Journal of Cancer 10 28775772
2015 Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent. Bioorganic & medicinal chemistry letters 10 26547690
2023 Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3. Phytomedicine : international journal of phytotherapy and phytopharmacology 8 38128397
2023 Predictive Value of PRISM-4, PIM-3, CRP, Albumin, CRP/Albumin Ratio and Lactate in Critically Ill Children. Children (Basel, Switzerland) 7 38002822
2020 High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms. Endocrine pathology 7 32504181
2019 Effect of Pim-3 Downregulation on Proliferation and Apoptosis in Lung Adenocarcinoma A549 Cells. Annals of clinical and laboratory science 7 31882428
2017 mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci. Scientific reports 7 29170467
2015 Overexpression of pim-3 and protective role in lipopolysaccharide-stimulated hepatic stellate cells. World journal of gastroenterology 7 26269675
2015 Binding site identification and role of permanent water molecule of PIM-3 kinase: A molecular dynamics study. Journal of molecular graphics & modelling 7 26529487
2021 LncRNA RGMB-AS1 facilitates pancreatic cancer cell proliferation and migration but inhibits cell apoptosis via miR-574-3p/PIM3 axis. American journal of physiology. Gastrointestinal and liver physiology 6 34468207
2019 Pim-3 alleviates lipopolysaccharide-stimulated AR42J pancreatic acinar cell injury via improving the inflammatory microenvironment. Experimental and therapeutic medicine 6 31777546
2017 Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling. Pathology, research and practice 6 28214201
2017 Expression and significance of Pim-3 kinase in adult T-cell leukemia. European journal of haematology 6 28833639
2014 Serine threonine kinase Pim-3 regulates STAT3 pathway to inhibit proliferation of human liver cancers. International journal of clinical and experimental medicine 6 24600488
2024 Endothelial Pim3 kinase protects the vascular barrier during lung metastasis. Nature communications 5 39627185
2023 PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis. Genes & genomics 5 38148455
2022 PIM3 kinase promotes tumor metastasis in hepatoblastoma by upregulating cell surface expression of chemokine receptor cxcr4. Clinical & experimental metastasis 5 36315303
2019 Downregulation of microRNA-124 prevents the development of acute liver failure through the upregulation of PIM-3. Experimental physiology 5 31628693
2025 ETS1 modulates ferroptosis to affect the process of myocardial ischemia-reperfusion injury via PIM3. Experimental cell research 4 40189183
2025 Metabolic reprogramming through PIM3 inhibition reverses hypoxia-induced CAR-T cell dysfunction in solid tumors. Journal of translational medicine 4 41199316
2022 Long non-coding RNA long intergenic non-protein coding RNA 1232 promotes cell proliferation, migration and invasion in bladder cancer via modulating miR-370-5p/PIM3 axis. Journal of tissue engineering and regenerative medicine 4 35338769
2022 Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis. Annals of translational medicine 4 35722357
2022 Multi-stage analysis of FOXM1, PYROXD1, hTERT, PPARA, PIM3, BMI1 and MCTP1 expression patterns in colorectal cancer. Gastroenterology and hepatology from bed to bench 4 35845311
2019 The serine-threonine kinase PIM3 is an aldosterone-regulated protein in the distal nephron. Physiological reports 4 31397090
2025 Pim3 up-regulation by YY1 contributes to diabetes-induced cardiac hypertrophy and heart failure. Iranian journal of basic medical sciences 3 39850120
2024 Low miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway. Frontiers in oncology 3 39507762
2007 [Protective role of Pim-3 gene in intestinal mucosa damaged by burn or lipopolysaccharide]. Zhonghua yi xue za zhi 3 18261321
2024 Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3. Bioorganic & medicinal chemistry letters 1 38199328
2023 LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis. Biochemical genetics 1 37248373
2023 Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3. bioRxiv : the preprint server for biology 1 38106118
2018 [Effects of endotoxin/lipopolysaccharide on early apoptosis of human neutrophil through PIM3]. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns 1 30481923
2016 [Expression and Significance of Pim-3 Gene in Acute Myeloid Leukemia]. Zhongguo shi yan xue ye xue za zhi 1 27150984
2012 [Inhibitive mechanisms of Pim-3 affecting fulminant hepatic apoptosis]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 23207234
1996 Low frequency of PIM3 gene in patients with monoclonal gammopathies. Human heredity 1 8666412
2026 miR-1307-5p mediates endothelial dysfunction and inflammation induced by acute coronary syndrome by targeting PIM3. Journal of cardiothoracic surgery 0 42106777
2026 Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis. Molecular genetics and genomics : MGG 0 42201413
2025 PIM3-mediated phosphorylation stabilizes myeloid leukemia factor 2 to promote metastasis in osteosarcoma. The Journal of clinical investigation 0 41090348
2025 PIM3 enhances nucleus pulposus cell function and extracellular matrix integrity via kinase-dependent activation of the Akt/mTOR signaling axis in intervertebral disc degeneration. Translational research : the journal of laboratory and clinical medicine 0 41478528
2007 [Construction of a recombinant Pim3-expressing plasmid and expression and activity thereof: experiment with rats]. Zhonghua yi xue za zhi 0 18067836

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