Affinage

PIM1

Serine/threonine-protein kinase pim-1 · UniProt P11309

Length
313 aa
Mass
35.7 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 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

PIM1 is a constitutively active serine/threonine kinase that phosphorylates substrates bearing a basic consensus motif [(Arg/Lys)3-X-Ser/Thr] to promote cell survival, cell cycle progression, and resistance to apoptotic and metabolic stress (PMID:1713213, PMID:1416988, PMID:16227208). Crystallographic and peptide-library analyses defined its substrate specificity and revealed an atypical mode of recognizing upstream basic residues, along with a non-canonical autophosphorylation site (PMID:16227208). Catalytically, PIM1 phosphorylates a broad set of effectors to drive proliferation and survival: it modifies p21Cip1 at Thr145 to control its stability and nuclear/cytoplasmic partitioning (PMID:12431783, PMID:17855660); activates Cdc25C to promote G2/M progression (PMID:16356754); phosphorylates RUNX1/RUNX3 to alter their transactivation, stability, and localization (PMID:16684349, PMID:18767071); phosphorylates HP1γ at Ser93 to enforce H3K9me3-dependent heterochromatin and senescence-associated gene silencing (PMID:25040935); and phosphorylates PRAS40 at Thr246 to relieve mTORC1 inhibition, coupling PIM1 to AMPK/mTORC1 control of translation (PMID:19276681, PMID:21187426). PIM1 enforces survival by phosphorylating ASK1 at Ser83 to suppress JNK/p38 and caspase-3 signaling (PMID:19749799) and, in cardiomyocytes, by upregulating Bcl-2/Bcl-XL, phosphorylating BAD, and preserving mitochondrial integrity downstream of AKT (PMID:18037896, PMID:20203306). PIM1 abundance is dynamically controlled: Hsp90 (and Hsp70) stabilize the active kinase while the ubiquitin-proteasome system, PP2A through its B56β subunit, and GSK-3β-mediated phosphorylation drive its degradation (PMID:11237709, PMID:15798097, PMID:17297438, PMID:33568357). Its transcription is induced by HOXA9 and by IL-6/STAT3 signaling, linking cytokine and oncogenic inputs to PIM1-dependent survival and senescence programs (PMID:17327400, PMID:25040935). Beyond its catalytic functions, PIM1 acts as a kinase-independent scaffold promoting assembly of TRIF/TRAF3/TBK1/IRF3 complexes to drive IRF3 activation and IFN-β production after TLR stimulation (PMID:36446848).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 High

    Establishing PIM1's enzymatic identity was the foundational question; the work showed it is exclusively a serine/threonine kinase with autophosphorylation activity and no tyrosine kinase activity.

    Evidence In vitro kinase assays with purified recombinant GST-PIM-1 on histone H1 and peptide substrates

    PMID:1713213

    Open questions at the time
    • Did not define physiological substrates
    • No structural basis for catalysis
  2. 1992 High

    Defining how PIM1 selects substrates answered the specificity question, establishing a basic-residue consensus motif and confirming activity via a kinase-dead control.

    Evidence In vitro peptide substrate profiling and Lys67Met active-site mutagenesis

    PMID:1416988

    Open questions at the time
    • Consensus derived from synthetic peptides, not endogenous substrates
    • No structural rationale until later
  3. 2005 High

    Crystal structures resolved the molecular basis for PIM1's recognition of upstream basic residues and mapped a non-canonical autophosphorylation site, grounding the consensus in atomic detail.

    Evidence Crystal structures with substrate peptide plus AMP-PNP or inhibitor, oriented peptide library screen, active-site mutagenesis

    PMID:16227208

    Open questions at the time
    • Static structures do not capture regulation of activity in cells
    • Did not address protein-level regulation
  4. 2002 High

    Identifying p21Cip1 as a PIM1 substrate connected the kinase to cell cycle control, showing phosphorylation at Thr145 governs p21 subcellular localization.

    Evidence In vitro kinase assay, co-IP, kinase-dead comparison, and subcellular fractionation; later refined with phospho-specific antibodies and knockdown

    PMID:12431783 PMID:17855660

    Open questions at the time
    • Apparent discrepancy in localization effect of Thr145 vs Ser146 phosphorylation
    • In vivo relevance across tissues not fully resolved
  5. 2005 Medium

    Linking PIM1 to Cdc25C and mitotic structures extended its cell cycle role to the G2/M transition and mitotic spindle apparatus.

    Evidence In vitro phosphorylation, co-localization, phosphatase assays, and GFP-fusion live imaging in mitotically arrested cells

    PMID:12111331 PMID:16356754

    Open questions at the time
    • Spindle-pole substrate phosphorylation sites incomplete
    • Single-lab observations
  6. 2007 High

    Identifying ASK1 phosphorylation at Ser83 and BAD inactivation established the molecular basis of PIM1-mediated anti-apoptosis under stress.

    Evidence In vitro and in vivo phosphorylation, site mutagenesis, downstream JNK/p38/caspase readouts; HOXA9-driven BAD phosphorylation with genetic rescue

    PMID:17327400 PMID:19749799

    Open questions at the time
    • Relative contribution of each survival substrate not quantified
    • Cell-type dependence unresolved
  7. 2009 High

    Phosphorylation of PRAS40 at Thr246 and subsequent AMPK/mTORC1 studies placed PIM1 within translational and metabolic control independently of AKT.

    Evidence In vitro kinase assay, co-IP showing mTOR complex disruption, inhibitor and Pim triple-knockout MEF metabolic and translation assays

    PMID:19276681 PMID:21187426

    Open questions at the time
    • Direct vs indirect contributions to AMPK regulation not fully separated
    • In vivo metabolic consequences in normal tissue unclear
  8. 2008 High

    Demonstrating PIM1's cardioprotective role via AKT, Bcl-2/Bcl-XL, mitochondrial integrity, and progenitor division extended its function to tissue regeneration and stress survival.

    Evidence Pim-1 knockout and cardiac-specific transgenic mice, infarction models, mitochondrial integrity assays, asymmetric division quantification

    PMID:18037896 PMID:20075333 PMID:20203306

    Open questions at the time
    • Mitochondrial substrates of PIM1 not defined
    • Mechanism of progenitor fate determination incomplete
  9. 2014 High

    Identifying HP1γ Ser93 phosphorylation revealed a chromatin-level function, coupling IL-6/STAT3-induced PIM1 to heterochromatin formation and senescence.

    Evidence Co-IP, in vitro site-specific phosphorylation, ChIP for H3K9me3, ectopic expression and knockdown inducing senescence

    PMID:25040935

    Open questions at the time
    • Genome-wide scope of PIM1-dependent heterochromatin not mapped
    • Reconciliation of pro-proliferative and pro-senescent roles unresolved
  10. 2010 Medium

    Multiple regulatory studies established how PIM1 protein levels are controlled, defining Hsp90/Hsp70 stabilization, ubiquitin-proteasome degradation, and PP2A/B56β-directed turnover, later extended by GSK-3β phosphorylation.

    Evidence Co-IP, geldanamycin and proteasome inhibitors, B56β knockdown with half-life measurement, GSK-3β inhibition and constitutive AKT experiments

    PMID:11237709 PMID:15798097 PMID:17297438 PMID:33568357

    Open questions at the time
    • E3 ligase directing PIM1 ubiquitination not identified
    • Hierarchy among regulatory inputs unclear
  11. 2022 Medium

    Distinguishing a kinase-independent scaffolding role showed PIM1 promotes IRF3-containing TLR signaling complexes for IFN-β production, broadening its function beyond catalysis.

    Evidence Pim1-/- macrophages and mice, kinase-dead comparison, co-IP of TRIF/TRAF3/TBK1/IRF3, poly(I:C) challenge; also implicated in RANKL/TAK1 osteoclast signaling

    PMID:21068407 PMID:36446848

    Open questions at the time
    • Structural basis of scaffolding contacts undefined
    • Extent of kinase-independent roles across pathways unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIM1 integrates its catalytic and scaffolding activities, and which substrates dominate in specific physiological versus oncogenic contexts, remains unresolved.
  • No unified substrate hierarchy across cell types
  • E3 ligase and full degradation circuitry incomplete
  • In vivo relevance of individual phosphorylation events not systematically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-4839726 Chromatin organization 1
Partners
ASK1CDC25CHP1ΓHSP90AA1HSP90AB1PRAS40RUNX1RUNX3

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Recombinant human PIM-1 protein exhibits exclusively serine/threonine kinase activity in vitro; it phosphorylates histone H1 (Km ~51 µM) and shows autophosphorylation activity. No tyrosine kinase activity was detected under any tested conditions. In vitro kinase assay with purified GST-PIM-1 fusion protein expressed in E. coli; substrates included histone H1 and various peptides; amino-terminal sequence analysis confirmed protein identity The Journal of biological chemistry High 1713213
1992 The substrate recognition sequence for PIM-1 kinase requires basic amino acid residues (Arg/Lys) on the amino-terminal side of the target Ser/Thr; optimal consensus is (Arg/Lys)3-X-Ser/Thr*-X'. A kinase-dead mutant (Lys67→Met) confirmed no contaminating kinase activity. In vitro kinase assays with synthetic peptide substrates and site-directed mutagenesis (Lys67Met active-site mutant); phosphopeptide analysis of histone H1 Archives of biochemistry and biophysics High 1416988
1998 PIM-1 protein binds to p100 (a c-Myb transcriptional coactivator) via yeast two-hybrid and co-immunoprecipitation in animal cells, directly phosphorylates p100 in vitro, and functions downstream of Ras to stimulate c-Myb transcriptional activity in a p100-dependent manner. Yeast two-hybrid screen; in vitro kinase assay; co-immunoprecipitation in animal cells; transcriptional reporter assay Molecular cell High 9809063
1999 PIM-1 and c-Myc synergize downstream of STAT3/gp130 signaling to drive G1-to-S cell cycle progression and anti-apoptosis; a kinase-defective PIM-1 mutant attenuates gp130-mediated cell proliferation; VCP (valosine-containing protein) was identified as a downstream target gene of PIM-1 signaling. Kinase-dead PIM-1 mutant overexpression; constitutive expression rescue experiments; expression of mutant VCP leading to apoptosis; cytokine receptor signaling assays Immunity Medium 10626893
2001 PIM-1 physically interacts with Hsp90α and Hsp90β; the Hsp90 inhibitor geldanamycin induces rapid degradation of PIM-1 and reduces its kinase activity, indicating Hsp90 stabilizes and maintains PIM-1 function. Co-immunoprecipitation; treatment with Hsp90 inhibitor geldanamycin; kinase activity assays Biochemical and biophysical research communications Medium 11237709
2002 PIM-1 associates with p21Cip1/WAF1, phosphorylates p21 in vitro (at residues 140-147 region) and in vivo, and co-transfection of wild-type PIM-1 with p21 results in cytoplasmic localization of p21, while kinase-dead PIM-1 results in nuclear localization; Thr145 is the phosphorylation site responsible for cytoplasmic localization. Pull-down assay; co-immunoprecipitation; in vitro kinase assay with recombinant proteins; phosphoamino acid assay; co-transfection with wild-type and kinase-dead PIM-1; subcellular fractionation Biochimica et biophysica acta High 12431783
2002 PIM-1 dynamically redistributes during the cell cycle: it localizes to nucleus and cytoplasm during interphase but moves to spindle poles during mitosis. PIM-1 phosphorylates NuMA in vitro and co-immunoprecipitates with NuMA, HP1β, dynein, and dynactin in mitotically arrested HeLa cells; kinase-dead PIM-1 does not co-localize with NuMA at spindle poles and promotes apoptosis. Confocal microscopy (live-cell GFP fusion); co-immunoprecipitation; in vitro kinase assay with immunoprecipitated NuMA; nocodazole-arrested mitotic cells Chromosoma Medium 12111331
2004 PIM-1 inhibits STAT5-dependent transcription by interacting with SOCS1 and SOCS3 and potentiating their inhibitory effects, most likely via phosphorylation-mediated stabilization of SOCS proteins; PIM-1 does not directly phosphorylate or bind STAT5. Ectopic expression in FDCP1 myeloid cells; STAT5 tyrosine phosphorylation and DNA-binding assays; co-immunoprecipitation of PIM-1 with SOCS1/SOCS3 Blood Medium 14764533
2005 Crystal structures of PIM-1 bound to a high-affinity peptide substrate with either AMP-PNP or a bisindolylmaleimide inhibitor revealed an unanticipated mode of recognition for basic residues upstream of the phosphorylation site. Peptide library screens defined PIM-1 substrate specificity, and the major site of PIM-1 autophosphorylation maps to a novel site diverging from its consensus phosphorylation motif. Crystal structure determination; oriented peptide library screen; in vitro kinase assays; active-site mutagenesis The Journal of biological chemistry High 16227208
2005 PIM-1 directly interacts with and phosphorylates the N-terminal region of Cdc25C, enhances Cdc25C phosphatase activity, and promotes progression through the G2/M checkpoint; PIM-1 and Cdc25C co-localize in the cytoplasm of epithelial and myeloid cells. Biochemical phosphorylation assays; immunofluorescence co-localization; transfection with bleomycin-induced G2/M arrest; phosphatase activity assays The international journal of biochemistry & cell biology Medium 16356754
2005 PIM-1 protein stability is regulated by Hsp90 (stabilizing) and the ubiquitin-proteasome pathway (degrading): PIM-1 is ubiquitinated and degraded by the proteasome; Hsp70 associates with PIM-1 targeted for degradation; Hsp90 inhibitor geldanamycin prevents heat-shock-mediated PIM-1 stabilization. PIM-1 kinase activity is maintained when bound to either Hsp70 or Hsp90. Immunoprecipitation to detect ubiquitinated PIM-1; proteasome inhibitor PS-341; Hsp90 inhibitor geldanamycin; luminescence-based kinase assay; pulse-chase half-life measurements Molecular cancer research : MCR Medium 15798097
2006 PIM-1 kinase phosphorylates RUNX1 and RUNX3 proteins and enhances RUNX1 transactivation activity in a dose-dependent manner; PIM-1 physically associates with RUNX1 and RUNX3 (co-precipitation and co-localization in cell culture), and this interaction was initially identified by yeast two-hybrid using the C-terminal part of RUNX3. Yeast two-hybrid; co-immunoprecipitation; co-localization by confocal microscopy; in vitro kinase assay; transcriptional reporter assay BMC cell biology Medium 16684349
2007 PIM-1 phosphorylates p21Cip1/WAF1 on Thr145 in vitro and in vivo; this phosphorylation promotes nuclear localization of p21 and its stabilization. Phosphorylation of Ser146 (indirect consequence of PIM-1 expression) promotes cytoplasmic localization. PIM-1 knockdown decreases proliferation of H1299 cells and soft agar growth. Site-directed mutagenesis of p21; phospho-specific antibodies; in vitro kinase assay with recombinant proteins; co-transfection; siRNA knockdown; immunofluorescence for subcellular localization Molecular cancer research : MCR High 17855660
2007 PP2A negatively regulates PIM-1 protein levels through the B56β regulatory subunit: PIM-1 co-immunoprecipitates specifically with B56β (not other B subunits); knockdown of B56β increases PIM-1 half-life from 0.7 to 2.8 h and decreases PIM-1 ubiquitination. Pin1 (prolyl-isomerase) also binds PIM-1 and decreases its protein level, potentially allowing PP2A/B56β interaction. Co-immunoprecipitation; shRNA knockdown of B56β; pulse-chase experiments; ubiquitination assays; PP2A catalytic subunit overexpression; okadaic acid inhibitor Oncogene Medium 17297438
2007 HOXA9 protein directly binds the PIM1 promoter and induces PIM1 mRNA and protein expression in hematopoietic cells; PIM1 induction by HOXA9 increases phosphorylation and inactivation of proapoptotic BAD; Hoxa9-/- cells show increased apoptosis and decreased proliferation that are rescued by reintroduction of PIM1. Chromatin immunoprecipitation (ChIP) of HOXA9 at PIM1 promoter; Western blot; retroviral reintroduction; apoptosis and proliferation assays in Hoxa9-/- cells Blood Medium 17327400
2007 PIM-1 is a crucial downstream effector of AKT-mediated cardioprotection; Pim-1 deficiency abrogates AKT-associated cardioprotection after myocardial infarction or pressure overload. Transgenic PIM-1 overexpression inhibits cardiomyocyte apoptosis with concomitant increases in Bcl-2, Bcl-XL protein levels, and Bad phosphorylation. PIM-1 overexpression is associated with increased SERCA2a expression and enhanced calcium dynamics. Pim-1 knockout mice; cardiac-specific Pim-1 transgenic mice; myocardial infarction model; Western blot for Bcl-2, Bcl-XL, pBad; calcium transient measurements; echocardiography Nature medicine High 18037896
2008 PIM-1 phosphorylates RUNX3 at four Ser/Thr residues within the Runt domain, stabilizes RUNX3 protein, and markedly alters RUNX3 cellular localization from the nucleus to the cytoplasm. In vitro phosphorylation assay; site-directed mutagenesis; co-immunoprecipitation; immunofluorescence subcellular localization; Western blot for protein stability Journal of cellular biochemistry Medium 18767071
2009 PIM1 directly phosphorylates PRAS40 at Thr246 (an AKT substrate site) independently of AKT activation; this phosphorylation reduces PRAS40 association with mTOR, thereby increasing mTOR-directed phosphorylation of 4EBP1 and p70S6K. PIM1 overexpression thus activates mTORC1 signaling. In vitro kinase assay with PRAS40; co-immunoprecipitation of PRAS40 with mTOR; Western blot for 4EBP1 and p70S6K phosphorylation; PIM1 kinase inhibitors; FDCP1 cell model Cancer biology & therapy High 19276681
2009 PIM1 phosphorylates ASK1 specifically on Ser83 both in vitro and in vivo; PIM1 binds ASK1 by co-immunoprecipitation; this phosphorylation decreases ASK1 kinase activity, inhibits downstream JNK and p38 phosphorylation, suppresses caspase-3 activation, and reduces H2O2-induced apoptosis. In vitro kinase assay; co-immunoprecipitation; site-specific mutagenesis (Ser83); Western blot for JNK/p38/caspase-3 phosphorylation; PIM1 siRNA knockdown; H2O2-induced oxidative stress Oncogene High 19749799
2010 PIM-1 directly interacts with and phosphorylates P-glycoprotein (Pgp/ABCB1); PIM-1 knockdown or inhibition decreases cellular and cell-surface 170-kDa Pgp with increased Pgp ubiquitination and proteasomal degradation; PIM-1 protects Pgp from proteolytic/proteasomal degradation and enables Pgp glycosylation and cell-surface translocation, thereby supporting drug efflux. GST pull-down; in vitro kinase assay; immunoblotting after cycloheximide treatment; flow cytometry; siRNA knockdown; glycosylation inhibitor (2-deoxy-D-glucose) Molecular pharmacology High 20460432
2010 PIM-1 kinase localizes to the mitochondrial fraction during ischemia/reperfusion; cardiac-specific overexpression of PIM-1 increases antiapoptotic Bcl-XL and Bcl-2, preserves inner mitochondrial membrane potential under oxidative stress, prevents calcium overload-induced mitochondrial swelling, and inhibits cytochrome c release from isolated mitochondria. Subcellular fractionation; Western blot; cardiac-specific transgenic overexpression; mitochondrial membrane potential assay; ultrastructural electron microscopy; cytochrome c release assay from isolated mitochondria Circulation research High 20203306
2010 PIM kinase inhibition or Pim-1 siRNA activates AMPK by elevating AMP/ATP ratios, which in turn suppresses mTORC1 activity; triple-knockout MEFs lacking all Pim kinases show activated AMPK, reduced protein synthesis, and decreased cap-dependent translation. Pim-3 expression alone in TKO MEFs reverses AMPK activation. Pim triple-knockout MEFs; SMI-4a kinase inhibitor; siRNA; AMPK/mTORC1 phosphorylation assays; metabolic (AMP/ATP) measurements; cap-dependent translation assay; Pim-3 re-expression Proceedings of the National Academy of Sciences of the United States of America High 21187426
2010 PIM-1 is destabilized under ribosomal stress (ribosomal protein deficiency induced by RNAi or nucleolar inhibition); reduced PIM-1 levels lead to increased p27Kip1 and cell cycle arrest independently of p53; restoring PIM-1 level by transfection recovers cell growth. PIM-1 was also found to interact with ribosomal protein S19 and co-sediment with ribosomes. RNAi knockdown of ribosomal proteins; nucleolar inhibitor treatment; Western blot; co-sedimentation with ribosomes; PIM-1 transfection rescue; p27Kip1 assay in p53-deficient context Oncogene Medium 20639905
2010 Cardiac-specific PIM-1 overexpression stimulates asymmetric division of cardiac progenitor cells (CPCs): PIM-1 transgenic hearts show 65% asymmetric CPC division (vs. 26% in controls after infarction), as assessed by polarization of the cell fate determinant Numb in mitotic phospho-histone-positive CPCs. BrdU/Ki-67/c-Myc proliferation markers; confocal microscopy quantification of Numb and α-adaptin polarization; cardiac-specific Pim-1 transgenic mice; myocardial infarction model Circulation research Medium 20075333
2014 PIM-1 interacts with heterochromatin protein 1γ (HP1γ) and phosphorylates it on Ser93; this phosphorylation enhances HP1γ binding to H3K9me3, resulting in heterochromatin formation and suppression of proliferative genes (CCNA2, PCNA). IL-6/STAT3 signaling induces PIM-1 expression during senescence, linking cytokine signaling to heterochromatin formation via PIM-1. Co-immunoprecipitation; in vitro phosphorylation assay; site-specific mutagenesis (Ser93); ChIP for H3K9me3; ectopic PIM-1 expression inducing premature senescence; siRNA knockdown Aging cell High 25040935
2021 PIM1 regulates lipid oxidative metabolism in myeloid-derived suppressor cells (MDSCs) via PPARγ-mediated activities; enforced PPARγ expression rescues metabolic and functional defects in Pim1-/- MDSCs; pharmacologic PIM kinase inhibition disrupts myeloid immunosuppressive function and enhances CD8+ T-cell antitumor immunity. Pim1 knockout mice; single-cell RNA sequencing; PPARγ overexpression rescue in Pim1-/- MDSCs; AZD1208 pharmacological inhibitor; bilateral tumor model Cancer immunology research Medium 33579728
2021 GSK-3β phosphorylates PIM-1L at Ser95 and PIM-1S at Ser4, targeting PIM-1 for proteasomal degradation; this is downstream of AKT inactivation by PP2A-activating drugs and constitutively active AKT blocks this degradation. PP2A-activating drug treatment; constitutively active myristoylated AKT1 expression; GSK-3β inhibition; Western blot for Pim-1 proteasomal degradation; site-specific phosphorylation analysis Molecular cancer therapeutics Medium 33568357
2022 PIM1 promotes IFN-β production by macrophages after TLR stimulation; PIM1 enhances IRF3 phosphorylation and nuclear translocation by promoting formation of signaling complexes composed of TRIF, TRAF3, TBK1, and IRF3 — this role is independent of PIM1 kinase activity. Pim1-/- mice produce less serum IFN-β after poly(I:C) challenge. Pim1-/- macrophages and mice; TLR3/TLR4 stimulation assays; IRF3 phosphorylation and nuclear translocation assays; co-immunoprecipitation of TRIF/TRAF3/TBK1/IRF3 complex; kinase-dead PIM1 experiments; poly(I:C) mouse challenge Experimental & molecular medicine Medium 36446848
2010 PIM-1 positively regulates RANKL-induced osteoclastogenesis; PIM-1 interacts with RANK and TAK1, and promotes RANKL-induced NF-κB activation via TAK1; overexpression of TAK1 rescues NF-κB activation in the presence of dominant-negative PIM-1. PIM-1 also regulates NFATc1 transcription and osteoclast-associated receptor expression. Dominant-negative PIM-1; RNA interference; overexpression of TAK1; co-immunoprecipitation of PIM-1 with RANK and TAK1; NF-κB and NFATc1 reporter assays; osteoclastogenesis assays Journal of immunology Medium 21068407

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity 357 10626893
2005 The serine/threonine kinase Pim-1. The international journal of biochemistry & cell biology 303 15694833
1998 Pim-1 kinase and p100 cooperate to enhance c-Myb activity. Molecular cell 218 9809063
2007 Pim-1 regulates cardiomyocyte survival downstream of Akt. Nature medicine 193 18037896
2001 Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. Journal of veterinary science 183 12441685
2002 Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. Biochimica et biophysica acta 173 12431783
2005 Structure and substrate specificity of the Pim-1 kinase. The Journal of biological chemistry 168 16227208
2009 Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. Journal of medicinal chemistry 148 19072652
1993 Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice. Proceedings of the National Academy of Sciences of the United States of America 122 7504280
2009 PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells. Cancer biology & therapy 117 19276681
1993 In vivo analysis of Pim-1 deficiency. Nucleic acids research 111 8233823
2007 Pim-1 kinase-dependent phosphorylation of p21Cip1/WAF1 regulates its stability and cellular localization in H1299 cells. Molecular cancer research : MCR 110 17855660
2011 The proto-oncogene Pim-1 is a target of miR-33a. Oncogene 108 21743487
2010 The Pim protein kinases regulate energy metabolism and cell growth. Proceedings of the National Academy of Sciences of the United States of America 108 21187426
2005 The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C. The international journal of biochemistry & cell biology 107 16356754
2004 Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3. Blood 106 14764533
2004 Pim-1 expression in prostatic intraepithelial neoplasia and human prostate cancer. The Prostate 106 15264249
2018 PIM Kinase as an Executional Target in Cancer. Journal of cancer prevention 101 30370255
2012 PIM1 kinase as a target for cancer therapy. Expert opinion on investigational drugs 99 22385334
2002 Pim-1 associates with protein complexes necessary for mitosis. Chromosoma 96 12111331
2015 Pim-1 kinase as cancer drug target: An update. Biomedical reports 95 26893828
2009 PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis. Oncogene 95 19749799
2010 Why target PIM1 for cancer diagnosis and treatment? Future oncology (London, England) 92 20919829
2005 Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Molecular cancer research : MCR 89 15798097
1991 Recombinant human pim-1 protein exhibits serine/threonine kinase activity. The Journal of biological chemistry 89 1713213
2010 Pim-1 kinase protects mitochondrial integrity in cardiomyocytes. Circulation research 88 20203306
2014 Pim kinases in hematological malignancies: where are we now and where are we going? Journal of hematology & oncology 79 25491234
2013 Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Neoplasia (New York, N.Y.) 79 23814490
2010 Pim-1 kinase protects P-glycoprotein from degradation and enables its glycosylation and cell surface expression. Molecular pharmacology 79 20460432
2015 Targeting the Pim kinases in multiple myeloma. Blood cancer journal 78 26186558
2014 MicroRNA-486-5p targeting PIM-1 suppresses cell proliferation in breast cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 77 25104088
2011 Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer science 75 21518143
2010 Cardiac progenitor cell cycling stimulated by pim-1 kinase. Circulation research 73 20075333
2018 The Natural Compound Myricetin Effectively Represses the Malignant Progression of Prostate Cancer by Inhibiting PIM1 and Disrupting the PIM1/CXCR4 Interaction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 72 30045021
2001 Regulation of Pim-1 by Hsp90. Biochemical and biophysical research communications 72 11237709
2007 Negative regulation of Pim-1 protein kinase levels by the B56beta subunit of PP2A. Oncogene 70 17297438
1992 Characterization of the proto-oncogene pim-1: kinase activity and substrate recognition sequence. Archives of biochemistry and biophysics 68 1416988
2023 Targeting Pim kinases in hematological cancers: molecular and clinical review. Molecular cancer 66 36694243
2019 PIM kinase inhibitors: Structural and pharmacological perspectives. European journal of medicinal chemistry 66 30954777
2012 The PIM kinases in hematological cancers. Expert review of hematology 66 22272708
2010 Pim kinase inhibitors: a survey of the patent literature. Expert opinion on therapeutic patents 66 20100002
2007 Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 66 18042805
2010 Overexpression of Pim-1 in bladder cancer. Journal of experimental & clinical cancer research : CR 64 21143989
2004 Role of pim-1 in smooth muscle cell proliferation. The Journal of biological chemistry 63 15471855
2007 Pim kinase substrate identification and specificity. Journal of biochemistry 61 17234686
2008 Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload. Proceedings of the National Academy of Sciences of the United States of America 60 18784362
2007 Evidence that the Pim1 kinase gene is a direct target of HOXA9. Blood 59 17327400
2015 PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma. Oncotarget 57 25834102
2011 The oncogenic PIM kinase family regulates drug resistance through multiple mechanisms. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 57 21601509
2021 Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer. Cancer immunology research 56 33579728
2000 Pim-1 kinase protects hematopoietic FDC cells from genotoxin-induced death. Oncogene 56 10951575
2017 PIM kinases: From survival factors to regulators of cell motility. The international journal of biochemistry & cell biology 54 29108877
2012 IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines. Pancreas 54 22273698
2010 PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression. Oncogene 53 20639905
2019 Pim-1 as a Therapeutic Target in Lupus Nephritis. Arthritis & rheumatology (Hoboken, N.J.) 51 30791224
2006 Pim-1 kinase phosphorylates RUNX family transcription factors and enhances their activity. BMC cell biology 51 16684349
2011 The Pim kinases: new targets for drug development. Current drug targets 50 21777193
2014 PIM-1 modulates cellular senescence and links IL-6 signaling to heterochromatin formation. Aging cell 49 25040935
2014 EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation. PLoS pathogens 47 25121590
2010 PIM kinase inhibitors downregulate STAT3(Tyr705) phosphorylation. Molecular cancer therapeutics 47 20667852
1996 Ubiquitous expression and cell cycle regulation of the protein kinase PIM-1. Archives of biochemistry and biophysics 47 8660654
2020 Resveratrol suppresses gastric cancer cell proliferation and survival through inhibition of PIM-1 kinase activity. Archives of biochemistry and biophysics 44 32473133
2017 Eco-friendly synthesis of novel cyanopyridine derivatives and their anticancer and PIM-1 kinase inhibitory activities. European journal of medicinal chemistry 42 28431341
2015 Targeting Pim kinases for cancer treatment: opportunities and challenges. Future medicinal chemistry 40 25582332
2013 Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation. Journal of virology 39 24155393
2009 Transcriptional regulation of Pim-1 kinase in vascular smooth muscle cells and its role for proliferation. Basic research in cardiology 39 19711112
2014 Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival. Neuro-oncology 38 25155357
2006 Up-regulation of a serine-threonine kinase proto-oncogene Pim-1 in oral squamous cell carcinoma. International journal of oral and maxillofacial surgery 38 16546353
2020 The role of Pim kinase in immunomodulation. American journal of cancer research 37 33414987
2010 Pim-1 regulates RANKL-induced osteoclastogenesis via NF-κB activation and NFATc1 induction. Journal of immunology (Baltimore, Md. : 1950) 37 21068407
2008 Pim-1 kinase phosphorylates and stabilizes RUNX3 and alters its subcellular localization. Journal of cellular biochemistry 37 18767071
2021 PIM Kinases in Multiple Myeloma. Cancers 30 34503111
2021 Utilization of cyanopyridine in design and synthesis of first-in-class anticancer dual acting PIM-1 kinase/HDAC inhibitors. Bioorganic chemistry 27 34959179
2019 PIM-1 kinase is a novel regulator of proinflammatory cytokine-mediated responses in rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology (Oxford, England) 27 30204915
2018 Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer. OncoTargets and therapy 27 30349298
2011 Pim-1 kinase inhibits pathological injury by promoting cardioprotective signaling. Journal of molecular and cellular cardiology 27 21255581
2009 Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction. Anesthesiology 27 19934869
2004 Expression, purification, crystallization and preliminary crystallographic analysis of human Pim-1 kinase. Acta crystallographica. Section F, Structural biology and crystallization communications 27 16508102
2019 PIM-1 kinase: a potential biomarker of triple-negative breast cancer. OncoTargets and therapy 26 31496730
2018 Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma. Oncotarget 26 29854306
2010 Cell-permeable carboxyl-terminal p27(Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase. The Journal of biological chemistry 25 21062737
2014 Use of regulators and inhibitors of Pim-1, a serine/threonine kinase, for tumour therapy (review). Molecular medicine reports 24 24737044
2006 Pim-1 kinase expression during murine mammary development. Biochemical and biophysical research communications 24 16712793
2018 Targeting Pim Kinases and DAPK3 to Control Hypertension. Cell chemical biology 23 30033129
2012 PIM1 gene cooperates with human BCL6 gene to promote the development of lymphomas. Proceedings of the National Academy of Sciences of the United States of America 23 22451912
2012 Inhibition of Pim-1 attenuates the proliferation and migration in nasopharyngeal carcinoma cells. Asian Pacific journal of tropical medicine 23 22840454
2019 A review on PIM kinases in tumors. Bioinformation 22 31359998
2024 PIM1 kinase and its diverse substrate in solid tumors. Cell communication and signaling : CCS 21 39487435
2022 Pim1 promotes IFN-β production by interacting with IRF3. Experimental & molecular medicine 21 36446848
2024 Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles. Journal of medicinal chemistry 20 38164076
2022 Inhibition of CEBPB Attenuates Lupus Nephritis via Regulating Pim-1 Signaling. Mediators of inflammation 20 36248187
2021 PP2A-activating Drugs Enhance FLT3 Inhibitor Efficacy through AKT Inhibition-Dependent GSK-3β-Mediated c-Myc and Pim-1 Proteasomal Degradation. Molecular cancer therapeutics 20 33568357
2018 Downregulation of PIM1 regulates glycolysis and suppresses tumor progression in gallbladder cancer. Cancer management and research 20 30464610
2015 Clinical and biological significance of PIM1 kinase in osteosarcoma. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20 26687194
2014 Regulation of prostate stromal fibroblasts by the PIM1 protein kinase. Cellular signalling 20 25451079
2009 PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications. International journal of experimental pathology 20 19878356
2009 Pim-1 kinase as activator of the cell cycle pathway in neuronal death induced by DNA damage. Journal of neurochemistry 20 19895669
2020 New cyanopyridine-based scaffold as PIM-1 inhibitors and apoptotic inducers: Synthesis and SARs study. Bioorganic chemistry 19 33099167
2014 Structure-based design of low-nanomolar PIM kinase inhibitors. Bioorganic & medicinal chemistry letters 19 25575657
2012 Insights from Pim1 structure for anti-cancer drug design. Expert opinion on drug discovery 19 23004574

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