Affinage

EEF1E1

Eukaryotic translation elongation factor 1 epsilon-1 · UniProt O43324

Round 2 corrected
Length
174 aa
Mass
19.8 kDa
Annotated
2026-04-28
130 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EEF1E1 (AIMP3/p18) is a multifunctional scaffolding subunit of the multi-aminoacyl-tRNA synthetase complex (MSC) that bridges translational regulation and the DNA damage response. Within the MSC, it is anchored to methionyl-tRNA synthetase (MRS), specifically binds Met-tRNA(i)(Met), and mediates its transfer to eIF2γ to support translation initiation; upon genotoxic stress, GCN2-dependent phosphorylation of MRS at Ser662 releases AIMP3, which translocates to the nucleus and directly activates ATM/ATR kinases through its C-terminal domain to induce p53-dependent tumor suppression (PMID:22867704, PMID:22106287, PMID:15680327, PMID:18343821). AIMP3 functions as a haploinsufficient tumor suppressor, coupling both DNA-damage and oncogenic signals to p53 activation, and its loss permits transformation with severe chromosomal instability (PMID:15680327, PMID:16849534). Overexpression of AIMP3 drives proteasome-dependent degradation of mature lamin A, causing progeroid phenotypes and accelerated cellular senescence in vivo, while its suppression under hypoxia promotes autophagy and delays senescence (PMID:20726853, PMID:30706629).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1996 Low

    Identification of p18 as a component of the MSC sharing a structural motif with EF-1H subunits raised the question of how this small protein contributes to translational machinery organization.

    Evidence cDNA cloning and sequence homology analysis of hamster p18

    PMID:8849690

    Open questions at the time
    • Sequence homology only; no direct binding data confirming EF-1H association
    • No functional assay for translational role
    • Hamster ortholog — relevance to human not experimentally shown
  2. 2005 High

    The discovery that AIMP3 translocates to the nucleus upon DNA damage, directly binds ATM/ATR, and is required for ATM-dependent p53 activation established a moonlighting tumor-suppressive function entirely distinct from its translational role.

    Evidence Mouse knockout/heterozygous models, co-immunoprecipitation with ATM/ATR, nuclear translocation assays, p53 induction upon knockdown and overexpression

    PMID:15680327

    Open questions at the time
    • Structural basis for ATM/ATR interaction not yet defined
    • Signal that triggers AIMP3 release from MSC not identified
    • Relative contribution of ATM vs ATR activation unclear
  3. 2006 High

    Extending the tumor suppressor paradigm, AIMP3 was shown to couple oncogenic Ras/growth factor signaling to p53 through differential ATM/ATR activation, with haploinsufficiency permitting transformation and chromosomal instability.

    Evidence AIMP3 heterozygous cell lines, siRNA knockdown, oncogene transformation assays, chromosomal analysis

    PMID:16849534

    Open questions at the time
    • Mechanism by which oncogenic stress is sensed by AIMP3 remains unknown
    • Whether AIMP3 loss cooperates with specific oncogenes in human cancers not tested
  4. 2008 High

    The 2.0 Å crystal structure of AIMP3 resolved two distinct domains and mutagenesis pinpointed the C-terminal surface as essential for ATM binding and p53 activation, providing the first structural framework for its tumor-suppressive mechanism.

    Evidence X-ray crystallography, site-directed mutagenesis, co-immunoprecipitation, p53 activation assay

    PMID:18343821

    Open questions at the time
    • No co-crystal structure of AIMP3–ATM complex
    • N-terminal domain function remains uncharacterized
    • Whether the same surface mediates MRS binding is unknown
  5. 2011 High

    The mechanism for AIMP3 release from the MSC was resolved: GCN2 phosphorylates MRS at Ser662 upon UV stress, causing a conformational change that simultaneously releases AIMP3 for nuclear translocation and suppresses global translation, coupling these two responses.

    Evidence UV irradiation, in vitro GCN2 kinase assay, phosphomimetic MRS-S662D mutants, co-immunoprecipitation, Met incorporation assay in stable HeLa lines

    PMID:22106287

    Open questions at the time
    • Whether other kinases or stimuli can trigger AIMP3 release is untested
    • Nuclear import mechanism (carrier, NLS) not defined
    • Quantitative relationship between MRS phosphorylation kinetics and AIMP3 release unknown
  6. 2012 High

    AIMP3's translational function was mechanistically defined: it selectively binds aminoacylated initiator Met-tRNA(i)(Met), forms a ternary complex with MRS and eIF2γ, and mediates transfer of charged tRNA to eIF2 for translation initiation.

    Evidence Filter-binding assay discriminating aminoacylated vs. uncharged tRNA, pull-down with eIF2γ, AIMP3 knockdown with Met incorporation readout

    PMID:22867704

    Open questions at the time
    • Structural basis of Met-tRNA(i)(Met) selectivity not resolved
    • Whether AIMP3 is rate-limiting for translation initiation under physiological conditions unclear
    • Handoff mechanism from AIMP3 to eIF2γ not reconstituted
  7. 2010 Medium

    Overexpression studies in transgenic mice revealed that excess AIMP3 causes progeroid aging by driving proteasome-dependent degradation of mature lamin A, linking AIMP3 dosage to nuclear lamina integrity and cellular senescence.

    Evidence Transgenic mouse model, Western blotting for lamin isoforms, proteasome inhibitor rescue, senescence assays

    PMID:20726853

    Open questions at the time
    • Direct physical interaction between AIMP3 and lamin A not demonstrated
    • E3 ligase mediating lamin A degradation not identified
    • Whether endogenous AIMP3 upregulation during normal aging drives this pathway is unknown
  8. 2014 Medium

    miR-543 and miR-590-3p were identified as direct post-transcriptional suppressors of AIMP3 that decline during mesenchymal stem cell senescence, establishing AIMP3 accumulation as a driver of stem cell aging.

    Evidence miRNA overexpression, luciferase 3'-UTR reporter assay, AIMP3 overexpression in hMSCs with senescence readout

    PMID:25465621

    Open questions at the time
    • Physiological relevance of miRNA-mediated regulation in vivo not confirmed
    • Whether AIMP3-driven senescence in hMSCs proceeds through ATM/p53 or lamin A pathway not resolved
  9. 2019 Medium

    Under hypoxia, HIF1α suppresses AIMP3 expression to promote autophagy and delay senescence, while Notch3 positively regulates AIMP3, positioning AIMP3 as a metabolic–senescence switch in mesenchymal stem cells.

    Evidence Hypoxia culture, RNA-seq, AIMP3 overexpression/knockdown, mitochondrial respiration and autophagy assays in hMSCs and AIMP3-transgenic mouse MSCs

    PMID:30706629

    Open questions at the time
    • Mechanism by which AIMP3 suppresses autophagy is not defined
    • Notch3–AIMP3 regulatory axis not validated at the promoter level
    • In vivo relevance of HIF1α–AIMP3 axis beyond cultured MSCs untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for AIMP3's selective recognition of aminoacylated initiator tRNA, the identity of the E3 ligase mediating AIMP3-dependent lamin A degradation, the nuclear import mechanism for released AIMP3, and whether AIMP3's translational and DNA-damage functions are coordinately regulated in vivo across tissues.
  • No co-crystal structure of AIMP3 with Met-tRNA(i)(Met) or ATM
  • E3 ligase for lamin A degradation not identified
  • In vivo tissue-specific regulation of dual functions not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-392499 Metabolism of proteins 2 GO:0003723 RNA binding 1 R-HSA-8953854 Metabolism of RNA 1
Partners
ATMATREIF2S3GCN2LMNAMARS1
Complex memberships
multi-aminoacyl-tRNA synthetase complex (MSC)

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The p18 component of the multisynthetase complex (EEF1E1/AIMP3) shares a ~90-amino-acid protein motif with the N-terminal moieties of the β and γ subunits of eukaryotic elongation factor EF-1H, suggesting that p18 contributes a structural template for association of the multisynthetase complex with EF-1H. cDNA cloning and sequence homology analysis of hamster p18 FEBS letters Low 8849690
2005 AIMP3/p18 (EEF1E1) functions as a haploinsufficient tumor suppressor that upregulates p53 in response to DNA damage; it is induced by and translocates to the nucleus upon DNA damage, directly interacts with ATM/ATR kinases, and the activity of ATM is dependent on the level of p18, indicating that p18 is required for ATM/ATR-mediated p53 activation. Mouse knockout/heterozygous models, nuclear translocation assay, co-immunoprecipitation with ATM/ATR, p53 induction assay with p18 depletion/overexpression Cell High 15680327
2006 AIMP3 (EEF1E1) couples oncogenic stress (growth factor or Ras signaling) to p53 activation to prevent cell transformation; single allelic loss of AIMP3 blocks growth factor- or Ras-dependent p53 induction, and AIMP3 haploinsufficient cells show susceptibility to transformation by Ras or Myc alone with severe chromosomal instability, demonstrating differential activation of ATM and ATR downstream of AIMP3. AIMP3 heterozygous cell lines, siRNA knockdown, oncogene transformation assays, chromosomal analysis Cancer research High 16849534
2008 The crystal structure of AIMP3/p18 was determined at 2.0 Å resolution, revealing two distinct domains linked by a 7-amino-acid peptide: an N-terminal 56-aa domain with two helices and three antiparallel β-strands, and a C-terminal 111-aa domain with five helices. Mutations at the C-terminal putative binding site abolished interaction between AIMP3 and ATM and abrogated AIMP3's ability to activate p53, identifying the residues critical for its tumor-suppressive activity. X-ray crystallography at 2.0 Å, site-directed mutagenesis, co-immunoprecipitation, p53 activation assay The Journal of biological chemistry High 18343821
2010 Overexpression of AIMP3/p18 (EEF1E1) in transgenic mice causes a progeroid phenotype with accelerated cellular senescence and nuclear morphology defects. Mechanistically, AIMP3 overexpression leads to proteasome-dependent degradation of mature lamin A (but not lamin C, prelamin A, or progerin), causing an imbalance in lamin A isoform stoichiometry resembling progeria. Transgenic mouse generation, cellular senescence assays, Western blotting for lamin isoforms, proteasome inhibitor experiments Aging cell Medium 20726853
2011 Methionyl-tRNA synthetase (MRS) serves as a cytosolic anchor for AIMP3/p18; upon UV irradiation, GCN2 kinase phosphorylates MRS at Ser662, inducing a conformational change that releases AIMP3 from MRS. Released AIMP3 translocates to the nucleus for DNA damage response, while the phosphorylated MRS loses tRNA(Met) binding and down-regulates global translation, revealing a dual coupling of translational inhibition and DNA repair. UV irradiation, GCN2 kinase assay, phosphomimetic MRS mutants (S662D), Co-IP, Met incorporation assay, stable HeLa cell lines Proceedings of the National Academy of Sciences of the United States of America High 22106287
2012 AIMP3/p18 (EEF1E1) specifically interacts with Met-tRNA(i)(Met) in vitro (but not with unacylated or Lys-charged tRNA(i)(Met)), discriminates initiator from elongator Met-tRNA, and forms a non-competitive complex with MRS and eIF2γ. AIMP3 knockdown reduces the level of Met-tRNA(i)(Met) bound to the eIF2 complex and decreases global protein synthesis, establishing AIMP3 as a mediator of charged initiator tRNA transfer from MRS to eIF2 for translation initiation. Filter-binding assay, pull-down assay, AIMP3 knockdown, Met incorporation assay Journal of molecular biology High 22867704
2014 miR-543 and miR-590-3p directly target AIMP3/p18 (EEF1E1) transcripts; their levels decrease during senescence in human mesenchymal stem cells (hMSCs) while AIMP3/p18 protein increases. AIMP3/p18 overexpression alone is sufficient to induce cellular senescence phenotypes including compromised clonogenicity and adipogenic differentiation potential, identifying AIMP3 as a regulator of cellular aging in hMSCs. miRNA overexpression, luciferase reporter with AIMP3 3'-UTR, AIMP3 overexpression in hMSCs, senescence assays Age (Dordrecht, Netherlands) Medium 25465621
2019 AIMP3 (EEF1E1) expression is suppressed by HIF1α under hypoxia in human placenta-derived mesenchymal stem cells, and this suppression is associated with induction of autophagy and delayed senescence. AIMP3 overexpression under hypoxia promotes mitochondrial respiration and suppresses autophagic activity, while AIMP3 downregulation ameliorates age-related senescence; Notch3 positively regulates AIMP3 expression. Hypoxia culture, RNA sequencing, AIMP3 overexpression/knockdown, mitochondrial respiration assay, autophagy assay in hMSCs and AIMP3-transgenic mouse MSCs Aging cell Medium 30706629
2019 Eef1e1 (EEF1E1/AIMP3) expression is upregulated in high-affinity TCR-stimulated mouse naive T cells compared to low-affinity T cells, and high Eef1e1 expression is associated with Th1/Th17 rather than T follicular helper cell differentiation, identifying Eef1e1 as a novel regulator of TCR affinity-dependent Th cell subset determination. TCR affinity-variant T cell transfer experiments, RNA-seq/gene expression profiling, in vivo infection model with bacteria expressing defined peptide Journal of immunology Low 30858199

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1994 Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes & development 765 8001816
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1995 Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Molecular and cellular biology 618 7739547
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1998 Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells. Leukemia 350 9639410
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1998 CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes & development 330 9744866
2012 Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. The Journal of biological chemistry 304 22685290
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
1995 Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer research 271 7882351
2009 The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes. The EMBO journal 270 19177150
1999 Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. The Journal of biological chemistry 268 10358062
2003 The DNA sequence and analysis of human chromosome 6. Nature 242 14574404
2000 Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis. The EMBO journal 225 10880462
2001 Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. The American journal of pathology 219 11485924
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
1995 Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood. Blood 171 7606004
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2001 Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced cell-cycle arrest in human hepatoma cell lines. Hepatology (Baltimore, Md.) 148 11343236
1997 Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6. Immunity 132 9052836
1994 Evolution of the Glx-tRNA synthetase family: the glutaminyl enzyme as a case of horizontal gene transfer. Proceedings of the National Academy of Sciences of the United States of America 131 8078941
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2005 The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell 121 15680327
1998 Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning. Proceedings of the National Academy of Sciences of the United States of America 119 9653160
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2021 FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2. Molecular cancer 106 33658012
2021 Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling. Molecular cell 105 33545068
2003 Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax. Blood 104 12816867
2011 Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proceedings of the National Academy of Sciences of the United States of America 103 22106287
2005 Hematopoietic stem cell exhaustion impacted by p18 INK4C and p21 Cip1/Waf1 in opposite manners. Blood 102 16234365
1994 Regulation of phosphoprotein p18 in leukemic cells. Cell cycle regulated phosphorylation by p34cdc2 kinase. The Journal of biological chemistry 100 8144611
2006 Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening. Journal of clinical microbiology 96 16597877
2001 Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and p19(Ink4d). Molecular and cellular biology 94 11287627
1996 Alterations of the p15, p16,and p18 genes in osteosarcoma. Cancer genetics and cytogenetics 92 8603340
2001 Antibacterial, antitumor and hemolytic activities of alpha-helical antibiotic peptide, P18 and its analogs. The journal of peptide research : official journal of the American Peptide Society 87 12005420
2002 CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells. Immunity 86 12196289
2003 Haploinsufficiency of p18(INK4c) sensitizes mice to carcinogen-induced tumorigenesis. Molecular and cellular biology 83 12556487
2009 CDK inhibitor p18(INK4c) is a downstream target of GATA3 and restrains mammary luminal progenitor cell proliferation and tumorigenesis. Cancer cell 81 19411068
1996 The p18 component of the multisynthetase complex shares a protein motif with the beta and gamma subunits of eukaryotic elongation factor 1. FEBS letters 71 8849690
1996 Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells. Cancer research 65 8640838
2003 Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells. British journal of cancer 64 12698196
2000 Cooperation of p27(Kip1) and p18(INK4c) in progestin-mediated cell cycle arrest in T-47D breast cancer cells. Molecular and cellular biology 64 10713180
2002 Posttranscriptional regulation of p18 and p27 Cdk inhibitor proteins and the timing of oligodendrocyte differentiation. Developmental biology 63 11969268
1998 The crystal structure of H-2Dd MHC class I complexed with the HIV-1-derived peptide P18-I10 at 2.4 A resolution: implications for T cell and NK cell recognition. Immunity 62 9729040
1990 Amino acid sequence and characterization of a heparin-binding neurite-promoting factor (p18) from bovine brain. The Journal of biological chemistry 62 2229039
2012 Free fatty acids block glucose-induced β-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18. Diabetes 61 22338094
2019 TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2. Journal of immunology (Baltimore, Md. : 1950) 56 30858199
2006 AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability. Cancer research 55 16849534
2014 miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18. Age (Dordrecht, Netherlands) 53 25465621
1996 Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers. International journal of cancer 53 8631583
2006 Characterization of the Babesia gibsoni P18 as a homologue of thrombospondin related adhesive protein. Molecular and biochemical parasitology 52 16675041
1996 Molecular analysis of the cyclin-dependent kinase inhibitor genes p15INK4b/MTS2, p16INK4/MTS1, p18 and p19 in human cancer cell lines. International journal of cancer 51 8938142
2018 UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity. eLife 50 30020076
2010 In silico structural and functional analysis of fragments of the ankyrin repeat protein p18(INK4c). Journal of biomolecular structure & dynamics 49 19916573
2009 P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development. International journal of cancer 48 18942719
2002 Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis. Leukemia 48 11840272
1996 Biochemical characterization of p16INK4- and p18-containing complexes in human cell lines. The Journal of biological chemistry 47 8663131
1996 Molecular analysis of the cyclin-dependent kinase inhibitor family: p16(CDKN2/MTS1/INK4A), p18(INK4C) and p27(Kip1) genes in neuroblastomas. Cancer 45 8630967
1996 A p18 mutant defective in CDK6 binding in human breast cancer cells. Cancer research 45 8840966
1995 Structural integrity of the cyclin-dependent kinase inhibitor genes, p15, p16 and p18 in myeloid leukaemias. British journal of haematology 45 7577621
2015 Small-molecule inhibitors targeting INK4 protein p18(INK4C) enhance ex vivo expansion of haematopoietic stem cells. Nature communications 43 25692908
1996 Complexity of the erythroid transcription factor NF-E2 as revealed by gene targeting of the mouse p18 NF-E2 locus. Proceedings of the National Academy of Sciences of the United States of America 43 8622968
1996 Homozygous deletions of cyclin-dependent kinase inhibitor genes, p16(INK4A) and p18, in childhood T cell lineage acute lymphoblastic leukemias. Leukemia 43 8637234
2008 Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme. Cancer research 42 18381405
2006 p18 Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control. Molecular and cellular biology 42 16738322
2001 An important role of CDK inhibitor p18(INK4c) in modulating antigen receptor-mediated T cell proliferation. Journal of immunology (Baltimore, Md. : 1950) 42 11544316
1996 Role of the cyclin-dependent kinase 4 and 6 inhibitor gene family p15, p16, p18 and p19 in leukemia and lymphoma. Leukemia & lymphoma 42 9031081
2011 The late endosome/lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes. Biochemical and biophysical research communications 40 22227194
2010 Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. Aging cell 40 20726853
2010 MEN-4 and other multiple endocrine neoplasias due to cyclin-dependent kinase inhibitors (p27(Kip1) and p18(INK4C)) mutations. Best practice & research. Clinical endocrinology & metabolism 39 20833334
2004 Reduced expression of cell cycle regulator p18(INK4C) in human hepatocellular carcinoma. Hepatology (Baltimore, Md.) 39 15349907
2012 AIMP3/p18 controls translational initiation by mediating the delivery of charged initiator tRNA to initiation complex. Journal of molecular biology 37 22867704
2013 The lysosomal signaling anchor p18/LAMTOR1 controls epidermal development by regulating lysosome-mediated catabolic processes. Journal of cell science 36 23781028
2008 Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development. Cancer research 36 18316595
2008 Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM. The Journal of biological chemistry 36 18343821
2003 The p18 truncated form of Bax behaves like a Bcl-2 homology domain 3-only protein. The Journal of biological chemistry 36 14681224
2014 p18/LAMTOR1: a late endosome/lysosome-specific anchor protein for the mTORC1/MAPK signaling pathway. Methods in enzymology 35 24377928
2006 A protective immune response is generated in rainbow trout by an OmpH-like surface antigen (P18) of Flavobacterium psychrophilum. Applied and environmental microbiology 35 16820479
1999 Tumor suppressor INK4: comparisons of conformational properties between p16(INK4A) and p18(INK4C). Journal of molecular biology 35 10556039
2019 HIF1α-mediated AIMP3 suppression delays stem cell aging via the induction of autophagy. Aging cell 33 30706629
1991 Regulated expression of p18, a major phosphoprotein of leukemic cells. The Journal of biological chemistry 33 1939149
1990 A gene that encodes for a leukemia-associated phosphoprotein (p18) maps to chromosome bands 1p35-36.1. Genes, chromosomes & cancer 33 2278968
1997 Parathyroid tumor suppressor on 1p: analysis of the p18 cyclin-dependent kinase inhibitor gene as a candidate. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 9286748
1988 Monoclonal antibodies to the human immunodeficiency virus p18 protein cross-react with normal human tissues. AIDS (London, England) 32 2456086
1987 Bacterial metabolism of alpha-pinene: pathway from alpha-pinene oxide to acyclic metabolites in Nocardia sp. strain P18.3. Journal of bacteriology 32 3667521
1993 Expression of the leukemia-associated gene, p18, in normal and malignant tissues; inactivation of expression in a patient with cleaved B cell lymphoma/leukemia. Oncogene 30 8397372
1996 Characterization of p18, a component of the lamin B receptor complex and a new integral membrane protein of the avian erythrocyte nuclear envelope. The Journal of biological chemistry 29 8647873
2009 Expression of p18(INK4C) is down-regulated in human pituitary adenomas. Endocrine pathology 28 19401813
2014 p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 25404710
2006 1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 26 16918598
2015 P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane. Oncoscience 25 25897432
2014 High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin. BMC cancer 25 24443788
2006 Simultaneous downregulation of CDK inhibitors p18(Ink4c) and p27(Kip1) is required for MEN2A-RET-mediated mitogenesis. Oncogene 25 16953232
2003 Suppression of ARG kinase activity by STI571 induces cell cycle arrest through up-regulation of CDK inhibitor p18/INK4c. Oncogene 25 12821941
1993 Envelope protein and p18(IIIB) peptide recognized by cytotoxic T lymphocytes from humans immunized with human immunodeficiency virus envelope. Vaccine 25 7688170
2007 Evaluation of CDKN2C/p18, CDKN1B/p27 and CDKN2B/p15 mRNA expression, and CpG methylation status in sporadic and MEN1-associated pancreatic endocrine tumours. Clinical endocrinology 24 17803708
2000 Frequent loss of 1p32 region but no mutation of the p18 tumor suppressor gene in meningiomas. Journal of neuro-oncology 24 11263500
1998 Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer. Biochemical and biophysical research communications 24 9636670
1996 The p16 and p18 tumor suppressor genes in neuroblastoma: implications for drug resistance. Cancer letters 24 8665486
2020 PRMT6 serves an oncogenic role in lung adenocarcinoma via regulating p18. Molecular medicine reports 23 32945431
2003 p18(INK4c) collaborates with other CDK-inhibitory proteins in the regenerating liver. Hepatology (Baltimore, Md.) 23 12668976
1995 Molecular analysis of a family of cyclin-dependent kinase inhibitor genes (p15/MTS2/INK4b and p18/INK4c) in non-small cell lung cancers. Molecular carcinogenesis 23 8519415
2016 CDKIs p18(INK4c) and p57(Kip2) are involved in quiescence of CML leukemic stem cells after treatment with TKI. Cell cycle (Georgetown, Tex.) 21 26985855
2014 Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. International journal of cancer 21 24917520
2011 Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease. BMC cancer 21 21595987
2005 Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration between the pRb and p53 pathways. Molecular carcinogenesis 21 15584024
2004 Activation of protein kinase C promotes human cancer cell growth through downregulation of p18(INK4c). Oncogene 20 15107819
1997 Analysis of the cyclin-dependent kinase inhibitors p18 and p19 in mantle-cell lymphoma and chronic lymphocytic leukemia. Annals of oncology : official journal of the European Society for Medical Oncology 20 9209645
1987 Purification and properties of alpha-pinene oxide lyase from Nocardia sp. strain P18.3. Journal of bacteriology 20 3667522
2006 Hematopoietic stem cells are not the direct target of spontaneous leukemic transformation in p18(INK4C)-null reconstituted mice. Cancer research 19 16397248
2001 Serological diagnosis of Epstein-Barr virus infection by novel ELISAs based on recombinant capsid antigens p23 and p18. Journal of medical virology 19 11241457
2017 The F1 -ATPase from Trypanosoma brucei is elaborated by three copies of an additional p18-subunit. The FEBS journal 18 29247468
2007 p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents. Cell cycle (Georgetown, Tex.) 18 17700068
1996 Mutational analysis of the joining regions flanking helix P18 in E. coli RNase P RNA. Journal of molecular biology 18 8676378