| 2001 |
The EMAPII cytokine domain of p43/AIMP1 is released from the multisynthetase complex after caspase-7 cleavage in vitro, and the released EMAPII domain can induce migration of human mononuclear phagocytes. The full-length p43/proEMAPII has strong tRNA binding capacity (KD = 0.2 µM), which is lost upon release of the EMAPII domain, suggesting cleavage limits tRNA availability for aminoacyl-tRNA synthetases in the complex. |
In vitro caspase-7 digestion assay, tRNA binding assay (Kd measurement), mononuclear phagocyte migration assay |
The Journal of biological chemistry |
High |
11306575
|
| 2001 |
Crystal structure of human EMAPII domain at 1.14 Å resolution reveals that it is a monomer consisting of an OB-fold (Trbp-like) domain and an extra domain related by degenerate 2-fold symmetry, mimicking the dimer interface of bacterial Trbp proteins, and generating a novel OB-fold-based tRNA-binding site. |
X-ray crystallography (1.14 Å resolution) |
The EMBO journal |
High |
11157763
|
| 2014 |
Crystal structure of the ArgRS–GlnRS–AIMP1 ternary subcomplex shows that the N-terminal helix of AIMP1 forms a coiled-coil with the N-terminal domain of ArgRS and anchors the C-terminal core of GlnRS. Mutation of AIMP1's N-terminal helix destabilizes ArgRS's N-terminal domain and abrogates ArgRS catalytic activity; mutation of ArgRS's N-terminal helix liberates GlnRS. AIMP1 also anchors the ternary complex to AIMP2/p38. |
X-ray crystallography, site-directed mutagenesis, aminoacylation activity assay, co-immunoprecipitation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25288775
|
| 2003 |
AIMP1/p43 is an integral component of both the nuclear and cytosolic human multisynthetase complexes, isolated to near homogeneity; gel filtration and immunoblot analysis demonstrate that a major biological role for p43 is as a structural part of the multisynthetase complex. |
Biochemical fractionation, gel filtration chromatography, immunoblotting, electron microscopy (negative staining) |
Protein science : a publication of the Protein Society |
Medium |
14500886
|
| 2006 |
Structural domain mapping of secreted AIMP1 using deletion fragments established three functionally distinct extracellular domains: aa 101–114 mediates pro-apoptotic activity toward endothelial cells (caspase-3 activation), aa 6–46 mediates fibroblast proliferation, and aa 114–192 mediates endothelial cell migration. |
Deletion fragment generation, endothelial cell death/caspase-3 assay, fibroblast proliferation assay, endothelial migration assay; elastase 2 cleavage |
Biochemical and biophysical research communications |
Medium |
16472771
|
| 2012 |
CD23 (low-affinity IgE receptor) was identified as the functional receptor for AIMP1 that mediates TNF-α secretion from THP-1 monocytic cells and primary human PBMCs. CD23 knockdown attenuated AIMP1 binding and AIMP1-induced TNF-α secretion. AIMP1-induced TNF-α secretion via CD23 involves ERK1/2 activation. Notably, the C-terminal EMAP II fragment of AIMP1 cannot bind CD23 or activate ERK1/2. |
Screen of 499 soluble receptors, co-immunoprecipitation, CD23 knockdown (siRNA), TNF-α ELISA, ERK1/2 phosphorylation assay, binding assay |
Journal of cell science |
High |
22767513
|
| 2010 |
TLR4 activation by LPS induces phosphorylation of AIMP1 at serine-140 by JNK (via MyD88 pathway), causing dissociation of AIMP1 from gp96 and resulting in increased gp96 cell surface expression. Alanine mutation of serine-140 suppressed LPS-induced gp96 surface presentation. |
TLR4/LPS stimulation, JNK inhibitor experiments, site-directed mutagenesis (S140A), co-immunoprecipitation, flow cytometry for gp96 surface expression |
Biochemical and biophysical research communications |
High |
20510162
|
| 2014 |
AIMP1 negatively regulates TGF-β signaling by interacting directly with Smad2 and Smad3, as demonstrated by co-immunoprecipitation and luciferase reporter assay. AIMP1 downregulation by siRNA promotes Smad2/3 phosphorylation and restores chondrogenic differentiation in dedifferentiated and OA-derived degenerated chondrocytes. |
Co-immunoprecipitation, luciferase reporter assay, siRNA knockdown, Western blot for p-Smad2/3, in vivo mouse implantation model |
Cell death & disease |
Medium |
26890138
|
| 2014 |
HCV envelope protein E2 directly interacts with AIMP1/p43 (by GST pulldown and co-immunoprecipitation) and promotes its degradation via ubiquitin-dependent proteasome pathway. E2 also disrupts the stabilizing interaction between AIMP1 and the ER chaperone grp78, further reducing cellular AIMP1. Loss of AIMP1 caused by E2 results in upregulation of TGF-β signaling and increased surface expression of gp96. |
GST pulldown, co-immunoprecipitation, confocal immunofluorescence, proteasome inhibitor experiments, TGF-β signaling assay, flow cytometry for gp96 surface expression |
PloS one |
Medium |
24816397
|
| 2006 |
EMAP-II pre-treatment of human endothelial cells does not increase TNF-R1 protein expression but induces redistribution of TNF-R1 from Golgi storage pools to the cell membrane and mobilizes TRADD to the membrane (in separate vesicles from TNF-R1), thereby sensitizing endothelial cells to TNF-induced apoptosis. |
Flow cytometry, immunofluorescence co-staining, Western blot, apoptosis assay |
Apoptosis : an international journal on programmed cell death |
Medium |
17051333
|
| 2000 |
Recombinant EMAP-II upregulates TNF-R1 (but not TNF-R2) mRNA and protein expression in human umbilical vein endothelial cells ~4-6 fold within 2 h, and conditioned media from high-EMAP-II expressing cell lines upregulated TNF-R1 by up to 20-fold; effect was blocked by anti-EMAP-II antibody. |
Northern blot/RT-PCR, ELISA, neutralizing antibody blockade |
Cytokine |
Medium |
10880244
|
| 2007 |
RARS overexpression impairs AIMP1 secretion in HeLa and MCF7 cells, and proteasome inhibition impairs cleavage of AIMP1 to generate mature EMAP II, indicating that the proteasome is involved in proteolytic processing of AIMP1 to produce EMAP II. |
RARS overexpression, proteasome inhibitor treatment, AIMP1/EMAP II detection (Western blot/ELISA) |
Journal of cellular physiology |
Medium |
17443684
|
| 2014 |
AIMP1 negatively regulates adipogenesis by directly interacting with the DNA-binding domain of PPARγ via co-immunoprecipitation, thereby inhibiting PPARγ transcriptional activity. AIMP1-deficient cells show augmented adipogenesis compared to controls. |
Co-immunoprecipitation, luciferase reporter assay, AIMP1 knockout/deficient cells, adipogenesis assay |
Journal of cell science |
Medium |
25146391
|
| 2011 |
Exogenous AIMP1 decreases endothelial cell viability through an α5β1 integrin-dependent mechanism and inhibits cell adhesion. Affinity purification, pulldown, and co-immunoprecipitation demonstrate that AIMP1 interacts with four cytoskeletal proteins: filamin-A, α-tubulin, vinculin, and cingulin. α-Tubulin is phosphorylated upon AIMP1 treatment, and AIMP1 colocalizes with filamin-A and cingulin. |
Affinity purification, pulldown, co-immunoprecipitation, immunofluorescence, integrin-blocking antibody, cell viability and adhesion assays |
Journal of cellular biochemistry |
Medium |
21416500
|
| 2015 |
AIMP1 promotes osteoclastogenesis and acts synergistically with RANKL; downregulation of CD23 (its receptor) abolishes AIMP1-mediated osteoclastogenesis, confirming that AIMP1 signals through CD23 to promote osteoclast differentiation. |
Osteoclastogenesis assay, CD23 knockdown, RANKL synergy assay, ELISA for serum AIMP1 in RA patients |
Biomaterials |
Medium |
25617125
|
| 2019 |
AIMP1 binds and colocalizes with FSCN1 (fascin) in laryngeal squamous cell carcinoma cells, as validated by co-immunoprecipitation/Western blotting and immunofluorescence; knockdown of AIMP1 inhibits LSCC cell proliferation, migration, and invasion. |
Co-immunoprecipitation, mass spectrometry, immunofluorescence, siRNA knockdown with proliferation/migration/invasion assays |
Proteomics |
Medium |
31287215
|
| 2022 |
In multiple myeloma, AIMP1 interacts with ANP32A (acidic leucine-rich nuclear phosphoprotein 32A) to regulate histone H3 acetylation, increasing H3 acetylation enrichment at the GAREM2 locus, which promotes p-ERK1/2 (MAPK pathway activation). AIMP1 also promotes osteoclast differentiation by activating NFATc1. |
Protein chip assay, co-immunoprecipitation, ChIP-seq, RNA-seq, MTT assay, xenograft model, TRAC staining |
Cancer communications (London, England) |
Medium |
36042007
|
| 2019 |
AIMP1 regulates T cell responses by inhibiting TCR-dependent activation: AIMP1 reduces lipid raft association upon TCR engagement, decreases Ca2+ influx, and downregulates phosphorylation of PLCγ and PI3K in CD4+ T cells. AIMP1 also specifically enhances differentiation of regulatory T (Treg) cells without affecting Th1, Th2, or Th17 differentiation. |
T cell activation assay, Ca2+ influx measurement, microscopic lipid raft analysis, Western blot for p-PLCγ/p-PI3K, Treg differentiation flow cytometry |
Biochemical and biophysical research communications |
Medium |
31084930
|
| 2018 |
AIMp1/p43 absence in bone marrow-derived dendritic cells impairs cytokine production, costimulatory molecule expression, p38 MAPK signaling, and TH1 polarization of co-cultured T cells. AIMp1-deficient DCs showed significantly compromised vaccine-mediated protection against melanoma in vivo, and AIMp1 in the host was critical for antiviral immunity against influenza. |
AIMp1 knockout BMDC, cytokine ELISA, flow cytometry for costimulatory molecules, p38 MAPK phosphorylation assay, T cell co-culture TH1 polarization assay, in vivo tumor and influenza models |
Frontiers in immunology |
Medium |
29379495
|
| 2012 |
AIMP1 deficiency in mice results in spontaneous airway hyperreactivity and TH2-biased immune responses; adoptive transfer of AIMP1-deficient CD4+ T cells to OVA-sensitized mice exacerbates airway inflammation. AIMP1-deficient mice show decreased serum IL-12p40, and AIMP1-deficient lung DCs show increased surface molecule expression, establishing AIMP1 as a negative regulator of TH2 responses in vivo. |
AIMP1-deficient mouse model, methacholine challenge (Penh values), adoptive transfer of CD4+ T cells, cytokine ELISA, histological analysis |
Clinical immunology (Orlando, Fla.) |
Medium |
22472603
|
| 2024 |
An AIMP1-derived peptide (TN41, aa 6–46) is generated by MMP1-mediated cleavage of AIMP1 secreted from Wnt-treated hair follicle stem cells, and this fragment activates dermal papilla cells by activating Akt and ERK, increasing β-catenin. TN41 promotes hair shaft elongation in cultured human hair follicles and enhances DPC spheroid hair-inducing activity. Deletion mapping identified aa 6–46 as the active region. |
Deletion mapping, MMP1 cleavage assay, Akt/ERK/β-catenin Western blot, hair follicle organ culture, DPC spheroid assay |
International journal of biological sciences |
Medium |
39494335
|
| 2025 |
AIMP1 derived from dopaminergic neurons is elevated in PD; Aimp1 knockout or knockdown improves DA neuron viability and reduces microglial activation in MPTP-induced PD mouse model. RNA-seq analysis revealed AIMP1 promotes microglial inflammatory response. AIMP1-induced microglial activation is CD23-dependent. |
MPTP mouse model, Aimp1 KO/KD, immunofluorescence for TH and microglia markers, RNA-seq, ELISA, in vitro MPP+ cell model |
CNS neuroscience & therapeutics |
Medium |
40522094
|
| 2025 |
EMAP-II packaged in macrophage-derived extracellular vesicles (from OGD/R-activated macrophages) is transferred to neutrophils, where it suppresses PI3K/AKT signaling, induces mitochondrial oxidative stress (mtROS), and drives pathological NETs formation in lung ischemia/reperfusion injury. shRNA-mediated EMAP-II knockdown in macrophages abolished OGD/R-EV-induced mtROS and NETs formation and mitigated pulmonary inflammation in mice. |
Proteomic profiling of EVs, shRNA EMAP-II knockdown, PI3K/AKT pharmacological inhibition, mtROS measurement, NETs assay, mouse LIRI model |
Redox biology |
Medium |
40616949
|
| 2025 |
AIMP1 functions as a limiter of autophagy, at least in part by uncoupling mTORC1 activity, while minimally affecting protein synthesis. Depletion of Aimp1 in murine myeloid cells impairs innate immunity kinetics, revealing that Aimp1's redundancy for protein synthesis allows it to reinforce autophagic activity. |
Gene essentiality genomics analysis, Aimp1 depletion in murine myeloid cells, transcriptomics, mTORC1 activity assays, innate immunity kinetics assay |
Communications biology |
Medium |
41862581
|
| 2011 |
AIMP1 upregulates TLR2 protein expression in bone marrow-derived DCs in a time- and dose-dependent manner via NF-κB activation (blocked by BAY11-7082), and enhances TLR2-mediated IL-6 and IL-12 production and costimulatory molecule expression when combined with TLR2 agonists. |
Flow cytometry, RT-PCR, NF-κB inhibitor (BAY11-7082), ELISA for IL-6/IL-12, costimulatory molecule expression assay |
Immunology |
Medium |
21711348
|
| 2025 |
AIMP1 downregulates the tight junction protein ZO-1 in brain microvascular endothelial cells, increasing blood-brain barrier permeability. siRNA knockdown of AIMP1 restored ZO-1 protein levels and reduced BBB permeability. The miRNA let-7f-5p directly targets AIMP1 (validated by luciferase reporter assay) and overexpression of let-7f-5p suppresses AIMP1 and partially rescues ZO-1 levels. |
siRNA knockdown, Western blot, luciferase reporter assay, Na-F permeability assay, TEER measurement |
Clinical and experimental immunology |
Medium |
41316924
|
| 2020 |
HLD3-associated frameshift mutant AIMP1 proteins (292CA) localize predominantly to lysosomes where they form aggregates and specifically interact with actin to block actin fiber formation; Q39X mutant also aggregates in lysosomes but without actin interaction. Both 292CA and Q39X mutants inhibit neuronal differentiation in N1E-115 cells; ibuprofen treatment reverses mutant-induced inhibitory differentiation and lysosomal localization. |
Immunofluorescence (lysosome/organelle localization), immunoprecipitation, actin fiber formation assay, neuronal differentiation assay, ibuprofen treatment |
Medicines (Basel, Switzerland) |
Medium |
32384815
|