Affinage

AIMP2

Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 · UniProt Q13155

Length
320 aa
Mass
35.3 kDa
Annotated
2026-06-09
49 papers in source corpus 24 papers cited in narrative 24 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

AIMP2 (JTV1/p38) is a structural scaffold of the multi-tRNA synthetase complex (MSC) that doubles as a stress-activated tumor suppressor and pro-apoptotic effector. As an MSC component, two AIMP2 N-terminal peptides form an antiparallel scaffold that holds two LysRS dimers, keeping all four catalytic subunits accessible for tRNA recognition, while its GST domain mediates conventional GST-type heterodimerization with EPRS and a strong contact with DRS that depends on AIMP2 Ser156 (PMID:30733335, PMID:31576228). Diverse stress signals — DNA damage, oxidative stress, and TGFβ (via S156 phosphorylation) — trigger AIMP2 dissociation from the MSC and nuclear translocation, where it executes several pro-death programs: it binds p53 to block MDM2-mediated ubiquitination, the p53 transactivation domain 1 docking onto the AIMP2 GST domain (PMID:18695251, PMID:32448505); it co-activates FBP/FUBP1-dependent transcription of the deubiquitinase USP29 to further stabilize p53 (PMID:21285945); it enhances Smurf2-mediated ubiquitination of FBP to suppress c-Myc (PMID:27197155); it competes with AXIN to inhibit Wnt/β-catenin signaling (PMID:27262173); and it binds TRAF2 to promote its c-IAP1-dependent degradation, sensitizing cells to TNFα-induced apoptosis (PMID:19584093). Consistent with these activities AIMP2 behaves as a haploinsufficient tumor suppressor (PMID:19622630). In dopaminergic neurons, accumulated AIMP2 directly associates with PARP1 in the nucleus to drive parthanatos, and also self-aggregates and seeds α-synuclein fibrillization, linking it to Parkinson's-relevant neurodegeneration (PMID:23974709, PMID:33177178). AIMP2 abundance is tightly controlled by parkin-mediated proteasomal degradation, VPS35/Lamp2a-dependent lysosomal clearance, HK2-driven autophagic degradation, and O-GlcNAcylation that stabilizes and aggregates it (PMID:16135753, PMID:28383562, PMID:34817071, PMID:37524692). An exon-2-deleted splice variant, AIMP2-DX2, antagonizes these tumor-suppressive functions by competing for p53, TRAF2, and PARP1 and by stabilizing KRAS against Smurf2-mediated degradation; DX2 itself is stabilized by HSP70, which shields it from Siah1-mediated ubiquitination (PMID:21483803, PMID:31792442, PMID:35546148, PMID:38172953). An AIMP2 nonsense mutation (Y35X) causes hypomyelinating leukodystrophy 17 through Golgi mislocalization and caspase-2-dependent oligodendroglial differentiation failure (PMID:34523057).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2005 High

    Established that AIMP2 abundance is degradation-controlled and that its accumulation is neurotoxic, framing AIMP2 as a parkin substrate relevant to dopaminergic survival.

    Evidence Co-IP, ubiquitination assay, parkin-knockout mice, and overexpression-induced catecholaminergic cell death rescued by wild-type but not R42P parkin

    PMID:16135753

    Open questions at the time
    • Did not define how accumulated AIMP2 kills neurons
    • Mechanism downstream of AIMP2 buildup unresolved at this stage
  2. 2008 High

    Answered how stress converts AIMP2 from a cytoplasmic scaffold into a nuclear apoptotic effector, defining the p53-stabilization axis.

    Evidence Co-IP, nuclear fractionation, MDM2 ubiquitination assay, and interaction-disrupting mutagenesis in AIMP2-deficient cells after genotoxic stress

    PMID:18695251

    Open questions at the time
    • Phosphorylation site driving dissociation not mapped here
    • Did not address other stress inputs
  3. 2009 High

    Showed AIMP2 also enforces apoptosis through a p53-independent route by destabilizing TRAF2 and dampening NF-κB.

    Evidence Reciprocal Co-IP of AIMP2-TRAF2 and TRAF2-c-IAP1, NF-κB reporters, and AIMP2 knockdown/knockout in TNFα-treated cells

    PMID:19584093

    Open questions at the time
    • How AIMP2 promotes c-IAP1-TRAF2 association mechanistically unclear
    • Stress signal coupling to this pathway not defined
  4. 2009 Medium

    Quantified the tumor-suppressive dosage of AIMP2, establishing it as haploinsufficient across multiple death/growth-arrest pathways.

    Evidence WT vs heterozygous vs homozygous AIMP2 cell comparison and carcinogen-induced tumorigenesis in heterozygous mice

    PMID:19622630

    Open questions at the time
    • Did not separate contributions of individual downstream pathways
    • Single lab
  5. 2011 High

    Connected oxidative stress to p53 stabilization via a transcriptional arm, adding USP29-mediated p53 deubiquitination to AIMP2's repertoire.

    Evidence Co-IP with FBP/FUBP1, fractionation, USP29 luciferase reporter, and USP29 deubiquitination assay on p53

    PMID:21285945

    Open questions at the time
    • How AIMP2 activates FBP transcriptionally not fully defined
    • Relation to direct p53 binding not integrated
  6. 2011 High

    Identified the oncogenic exon-2-deleted variant AIMP2-DX2 as a dominant antagonist that competes for p53 binding.

    Evidence Competitive Co-IP with p53, colony formation, cell death assays, and carcinogen-induced tumorigenesis in transgenic mice

    PMID:21483803

    Open questions at the time
    • How DX2 splicing is regulated in cancer not addressed
    • DX2 effects on non-p53 partners not yet explored here
  7. 2013 High

    Defined the mechanism of AIMP2-driven dopaminergic neurodegeneration as DNA-damage-independent PARP1 overactivation (parthanatos).

    Evidence AIMP2 transgenic mice, nuclear AIMP2-PARP1 Co-IP, and PARP1 genetic deletion/inhibitor rescue with behavioral and neuron-count readouts

    PMID:23974709

    Open questions at the time
    • How AIMP2 activates PARP1 structurally unresolved
    • Trigger for AIMP2 nuclear accumulation in neurons not defined
  8. 2014 High

    Revealed a proviral function in which AIMP2 stabilizes influenza M1 by switching its modification from ubiquitination to SUMOylation.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP with NS2, K242 mutagenesis, modification assays, and viral replication readout

    PMID:25320310

    Open questions at the time
    • How AIMP2 directs the ubiquitin-to-SUMO switch mechanistically unclear
    • Relevance to MSC dissociation not addressed
  9. 2016 High

    Mapped the TGFβ-responsive phospho-switch (S156) and showed AIMP2 suppresses c-Myc through Smurf2-mediated FBP ubiquitination.

    Evidence Phosphorylation mapping, fractionation, Co-IP of AIMP2-Smurf2 and Smurf2-FBP, FBP ubiquitination, S156 mutagenesis, and in vivo tumorigenesis

    PMID:27197155

    Open questions at the time
    • Kinase responsible for S156 phosphorylation not identified
    • Interplay with FBP's role in USP29 transcription not reconciled
  10. 2016 High

    Added a Wnt-suppressive role, showing AIMP2 competes with AXIN for DVL1 to restrain intestinal stem-cell expansion and adenoma formation.

    Evidence Competitive Co-IP of AXIN-DVL1, Aimp2 hemizygous mice, ApcMin/+ crosses, and intestinal organoids

    PMID:27262173

    Open questions at the time
    • How nuclear vs cytoplasmic AIMP2 pools are partitioned among pathways unclear
    • Stress dependence of Wnt suppression not defined
  11. 2019 High

    Provided structural definition of AIMP2's scaffolding role within the MSC and the basis for disease-causing LysRS release.

    Evidence 1.88 Å crystal structure of LysRS-AIMP2 plus gel filtration, Co-IP, and disease-mutation mapping; and crystal structure of the DRS-AIMP2GST-EPRSGST subcomplex with S156 mutagenesis

    PMID:30733335 PMID:31576228

    Open questions at the time
    • Structural transition accompanying stress-induced MSC dissociation not captured
    • Conformation of nuclear AIMP2 unknown
  12. 2019 High

    Explained how the oncogenic DX2 variant accumulates, identifying HSP70 as a chaperone that blocks Siah1-mediated DX2 degradation.

    Evidence Interactome analysis, X-ray crystallography, NMR, Co-IP, Siah1 ubiquitination assay, in vivo progression, and a DX2-HSP70 small-molecule inhibitor

    PMID:31792442

    Open questions at the time
    • Whether HSP70 similarly affects full-length AIMP2 not resolved
    • In vivo therapeutic window of the inhibitor not defined
  13. 2020 High

    Demonstrated AIMP2 self-aggregation and direct α-synuclein seeding, linking AIMP2 to proteinopathy in Parkinson's-relevant models.

    Evidence In vitro aggregation and binding assays, co-expression cell and mouse models, and AIMP2 knockdown rescue of fibril-/6-OHDA-induced death

    PMID:33177178

    Open questions at the time
    • Structural determinants of AIMP2 amyloid-like oligomerization not defined
    • Relation between aggregation and PARP1 activation not integrated
  14. 2020 Medium

    Resolved the structural basis for p53 recognition, mapping p53 TAD1 binding to the AIMP2 GST domain shared with DX2.

    Evidence NMR chemical-shift perturbation, transferred-NOE structure determination, and computational docking

    PMID:32448505

    Open questions at the time
    • Docking component is computational
    • Affinity comparison with MDM2-bound p53 not quantified in cells
  15. 2021 Medium

    Connected post-translational modification to AIMP2 stability and aggregation, showing O-GlcNAcylation drives PARP1 activation in hepatic steatosis.

    Evidence LC-MS proteomics, O-GlcNAcase knockout mice, OGT overexpression/OGA inhibition, and PARP1 activation assay

    PMID:34817071

    Open questions at the time
    • O-GlcNAc site(s) on AIMP2 not mapped
    • Tissue specificity beyond liver not tested
  16. 2021 Medium

    Linked AIMP2 to a Mendelian disease, showing the Y35X nonsense mutation causes HLD17 via Golgi mislocalization and caspase-2-dependent myelination failure.

    Evidence Immunofluorescence localization, caspase-2 activity assay, oligodendroglial differentiation phenotype, and CASP2 knockdown rescue

    PMID:34523057

    Open questions at the time
    • How a truncated protein reaches the Golgi mechanistically unclear
    • Relationship to MSC scaffolding loss not addressed
  17. 2022 High

    Expanded DX2 oncogenicity to RAS signaling, showing DX2 stabilizes pre-farnesylation KRAS by blocking Smurf2 access.

    Evidence Co-IP and domain mapping of DX2-KRAS, Smurf2 competition, in vitro binding, a DX2-KRAS inhibitor, and xenografts

    PMID:35546148

    Open questions at the time
    • Whether full-length AIMP2 also engages KRAS not established
    • Effect on downstream RAS effector pathways not detailed
  18. 2022 Medium

    Placed AIMP2 in an ALS pathway, showing mutant SOD1 binding to KARS1 releases AIMP2 to trigger TRAF2 degradation and neuronal death, antagonized by DX2.

    Evidence Co-IP of mutant SOD1-KARS1-AIMP2, TRAF2 degradation assay, ALS mouse model, and AAV-DX2 intrathecal rescue

    PMID:36242734

    Open questions at the time
    • Direct contribution of free AIMP2 vs other factors to motor neuron death not isolated
    • Single lab
  19. 2023 Medium

    Added a cancer-relevant degradation route, showing HK2-driven autophagic clearance of AIMP2 confers radio-resistance in hepatocellular carcinoma.

    Evidence HK2-AIMP2 Co-IP, autophagy inhibition, HK2 knockdown with apoptosis readout, and xenografts

    PMID:37524692

    Open questions at the time
    • How HK2 routes AIMP2 to autophagy mechanistically unclear
    • Interplay with other AIMP2 degradation systems not compared
  20. 2024 Medium

    Revised the DX2-PARP1 relationship, showing DX2 outcompetes AIMP2 for PARP1 to inhibit parthanatos, with therapeutic benefit in a Parkinson's model.

    Evidence Comparative Co-IP of AIMP2 vs DX2 with PARP1, nuclear translocation imaging, PARP1 activation assay, and AAV-DX2 rescue in 6-OHDA mice

    PMID:38172953

    Open questions at the time
    • How DX2's higher PARP1 affinity arises structurally not defined
    • Long-term safety of DX2 delivery not addressed
  21. 2024 Medium

    Generalized AIMP2's Smurf2-recruiting activity to antiviral defense, showing it degrades the EV71 3D polymerase.

    Evidence Co-IP of AIMP2-3D polymerase and AIMP2-SMURF2, ubiquitination assay, and viral replication with knockdown/overexpression

    PMID:38945214

    Open questions at the time
    • How AIMP2 distinguishes viral substrates for Smurf2 recruitment unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single scaffold partitions among its many mutually exclusive nuclear functions (p53, FBP/USP29, Smurf2/FBP, AXIN, TRAF2, PARP1) and what structural state AIMP2 adopts upon stress-induced MSC release and aggregation.
  • No structure of stress-released or nuclear AIMP2
  • Determinants selecting among competing partners undefined
  • Kinases/signals targeting each modification not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2
Partners
FUBP1KARS1PARP1SMURF2SNCATP53TRAF2VPS35
Complex memberships
multi-tRNA synthetase complex (MSC)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 AIMP2/p38 is a substrate of the E3 ubiquitin ligase parkin; parkin directly interacts with AIMP2, ubiquitinates it, and targets it for proteasomal degradation. Loss of parkin leads to accumulation of AIMP2 in the ventral midbrain/hindbrain, and overexpression of AIMP2 induces catecholaminergic cell death that is blocked by wild-type parkin but not by the familial R42P parkin mutant. Co-immunoprecipitation, ubiquitination assay, parkin knockout mouse analysis, adenovirus-mediated overexpression in substantia nigra, cell death rescue assay The Journal of neuroscience High 16135753
2008 Upon DNA damage (genotoxic stress), AIMP2 is phosphorylated, dissociates from the multi-tRNA synthetase complex (MSC), and translocates to the nucleus where it directly interacts with p53, thereby preventing MDM2-mediated ubiquitination and degradation of p53, and promoting apoptosis. Mutations in AIMP2 that disrupt its interaction with p53 abolish this pro-apoptotic activity. Co-immunoprecipitation, cell fractionation/nuclear translocation assay, AIMP2-deficient cell complementation, MDM2 ubiquitination assay, site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18695251
2009 AIMP2 promotes TNFα-dependent apoptosis by binding to TRAF2 and augmenting the association of the E3 ubiquitin ligase c-IAP1 with TRAF2, leading to ubiquitin-dependent degradation of TRAF2 and consequent suppression of NF-κB signaling. AIMP2-deficient cells show compromised TNFα-induced cell death. Co-immunoprecipitation (AIMP2–TRAF2 and TRAF2–c-IAP1), AIMP2 knockdown/knockout cell analysis, NF-κB/IκB reporter assay, ubiquitination assay Journal of cell science High 19584093
2009 AIMP2 exhibits haploinsufficiency as a tumor suppressor: heterozygous AIMP2 cells show dose-dependent reduction in apoptotic responses to DNA damage and TNFα, and reduced sensitivity to TGF-β-mediated growth arrest, with heterozygous mice showing increased susceptibility to carcinogen-induced tumorigenesis. Wild-type vs. hetero- vs. homozygous AIMP2 cell comparison, in vivo carcinogenesis models Carcinogenesis Medium 19622630
2011 In response to oxidative stress, AIMP2/JTV1 dissociates from the multi-tRNA synthetase complex, translocates to the nucleus, and associates with the transcription factor FBP (FUBP1) to co-activate transcription of USP29, a deubiquitinating enzyme that cleaves poly-ubiquitin chains from p53, stabilizing p53 and inducing apoptosis. Co-immunoprecipitation, subcellular fractionation/nuclear translocation, luciferase reporter assay for USP29 transcription, deubiquitination assay for USP29 activity on p53 The EMBO journal High 21285945
2011 An alternatively spliced variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed in human lung cancer cells. AIMP2-DX2 competes with full-length AIMP2 for binding to p53, thereby compromising AIMP2's pro-apoptotic activity and promoting anchorage-independent growth and resistance to cell death. Competitive binding/Co-immunoprecipitation with p53, colony formation assay, carcinogen-induced tumorigenesis in transgenic mice, cell death assay PLoS genetics High 21483803
2013 Transgenic overexpression of AIMP2 causes selective, age-dependent, progressive loss of dopaminergic neurons via direct physical association of AIMP2 with PARP1 in the nucleus, leading to PARP1 overactivation (parthanatos) independent of DNA damage. Genetic deletion or pharmacological inhibition of PARP1 rescues behavioral deficits and dopaminergic neuron loss in AIMP2 transgenic mice. AIMP2 transgenic mouse model, co-immunoprecipitation (AIMP2–PARP1 nuclear association), PARP1 knockout/inhibitor rescue experiments, behavioral testing, dopaminergic neuron counting Nature neuroscience High 23974709
2014 During influenza A virus infection, AIMP2 interacts with viral NS2 protein (identified by yeast two-hybrid, GST pulldown, and Co-IP). AIMP2 enhances stability of the viral matrix protein M1 by facilitating a switch from ubiquitination to SUMOylation at K242 of M1, thereby promoting viral ribonucleoprotein complex nuclear export and increasing viral replication. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, site-directed mutagenesis (K242), ubiquitination/SUMOylation assay, viral replication assay Journal of virology High 25320310
2016 TGFβ signaling causes phosphorylation of AIMP2 at S156, promoting its dissociation from the MSC and nuclear translocation. In the nucleus, phospho-AIMP2 binds Smurf2 and enhances Smurf2-mediated ubiquitination of FBP (FUBP1), a transcriptional activator of c-Myc, thereby suppressing c-Myc expression. AIMP2 also inhibits nuclear export of Smurf2 to sustain TGFβ signaling. Phosphorylation assay, nuclear fractionation, co-immunoprecipitation (AIMP2–Smurf2, Smurf2–FBP), ubiquitination assay for FBP, site-directed mutagenesis (S156), in vivo tumorigenesis assay Cancer research High 27197155
2016 AIMP2 disrupts the interaction between AXIN and Dishevelled-1 (DVL1) by competing with AXIN, thereby inhibiting Wnt/β-catenin signaling. Hemizygous deletion of Aimp2 results in enhanced Wnt/β-catenin signaling, increased crypt epithelial cell proliferation, expansion of intestinal stem cell compartments, and increased adenoma formation in ApcMin/+ mice. Co-immunoprecipitation (AXIN–DVL1 competition assay), Aimp2 hemizygous mouse model, ApcMin/+ crossed with Aimp2+/- mice, intestinal organoid assay Cancer research High 27262173
2017 VPS35 co-immunoprecipitates with AIMP2 and with lysosome-associated membrane protein-2a (Lamp2a), facilitating lysosomal degradation of AIMP2. The PD-associated VPS35 D620N mutant disrupts this association. VPS35 overexpression prevents AIMP2-potentiated PARP1 activation and cell death; VPS35 knockdown causes AIMP2-dependent PARP1 activation and cell death. Co-immunoprecipitation (VPS35–AIMP2, VPS35–Lamp2a), VPS35 overexpression/knockdown, PARP1 activation assay, cell death assay, VPS35 D620N mutant analysis Cell death & disease Medium 28383562
2019 Crystal structure (1.88 Å) of human LysRS in complex with AIMP2 reveals that two AIMP2 N-terminal peptides form an antiparallel scaffold holding two LysRS dimers through four binding motifs. This assembly allows all four LysRS catalytic subunits to remain accessible for tRNA recognition. Two human disease-associated mutations conflict with this assembly and cause LysRS release from the MSC. X-ray crystallography (1.88 Å), gel-filtration chromatography, co-immunoprecipitation, molecular modeling, disease mutation analysis The Journal of biological chemistry High 30733335
2019 Crystal structure of the DRS–AIMP2GST–EPRSGST ternary subcomplex shows that AIMP2GST and EPRSGST interact via conventional GST heterodimerization, while DRS strongly interacts with AIMP2GST via hydrogen bonds between the α7-β9 loop of DRS and the β2-α2 loop of AIMP2GST, with AIMP2 Ser156 being essential for this assembly. X-ray crystallography, structural analysis, site-directed mutagenesis (S156) IUCrJ High 31576228
2019 HSP70 is a critical determinant of AIMP2-DX2 cellular levels. HSP70 recognizes the N-terminal flexible region and GST domain of AIMP2-DX2 via its substrate-binding domain, blocking Siah1-dependent ubiquitination of AIMP2-DX2 and thereby stabilizing it. HSP70 augments AIMP2-DX2-induced cell transformation and cancer progression in vivo. Interactome analysis, X-ray crystallography, NMR, Co-immunoprecipitation, Siah1 ubiquitination assay, in vivo cancer progression assay, small molecule inhibitor of AIMP2-DX2–HSP70 interaction Nature chemical biology High 31792442
2020 AIMP2 exhibits self-aggregating (amyloid-like oligomerization) properties and directly binds α-synuclein monomer, seeding α-synuclein fibril formation. Co-expression of AIMP2 and α-synuclein in vitro and in vivo accelerates α-synuclein aggregation and increases toxicity. AIMP2 knockdown ameliorates α-synuclein aggregation and dopaminergic cell death in response to preformed fibril seeding or 6-OHDA. In vitro aggregation assay, direct binding assay (AIMP2–α-synuclein), co-expression cell model, in vivo mouse model, AIMP2 knockdown with cell death readout, fractionation into soluble/insoluble fractions Science translational medicine High 33177178
2020 NMR spectroscopy reveals that the transactivation domain 1 (TAD1) of p53 (residues E17–E28) binds to the GST domain of AIMP2 (shared with AIMP2-DX2). The p53 TAD1 adopts a turn structure with hydrophobic interactions by F19, L22, W23, and L26 upon binding, distinct from its MDM2-binding conformation. NMR chemical shift perturbation (CSP), transferred-NOE (trNOE) structure determination, computational docking Biochemical and biophysical research communications Medium 32448505
2021 O-GlcNAcylation of AIMP2 (mediated by O-GlcNAc transferase, OGT) increases AIMP2 protein stability and promotes its aggregation, leading to PARP1 activation in aging-related hepatic steatosis. O-GlcNAcase knockout increases AIMP2 and PARP1 levels in mouse liver. Comparative proteomics (LC-MS), O-GlcNAcase knockout mouse model, OGT overexpression and O-GlcNAcase inhibition in vitro, PARP1 activation assay FEBS letters Medium 34817071
2021 HLD17-associated nonsense mutation Y35X of AIMP2 causes mislocalization of AIMP2 protein to Golgi bodies as aggregates (wild-type AIMP2 distributes throughout the cell body), activates Golgi stress signaling via caspase-2, and inhibits oligodendroglial cell morphological differentiation. Knockdown of CASP2 reverses the differentiation defect caused by Y35X mutant AIMP2. Immunofluorescence localization, caspase-2 activity assay, differentiation phenotype assay, CASP2 knockdown rescue Neurochemical research Medium 34523057
2022 AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation, competitively blocking Smurf2 access to KRAS and thereby preventing ubiquitin-mediated KRAS degradation. This stabilizes KRAS and augments KRAS-driven tumorigenesis. Co-immunoprecipitation (AIMP2-DX2–KRAS, competition with Smurf2), domain mapping, in vitro binding assay, small molecule inhibitor of AIMP2-DX2–KRAS interaction, in vivo xenograft model Nature communications High 35546148
2022 Binding of mutant SOD1 (ALS-associated) to LysRS (KARS1) releases AIMP2 from its KARS1-containing complex; free AIMP2 then induces TRAF2 degradation and TNFα-induced neuronal cell death. AIMP2-DX2 competes with full-length AIMP2 for TRAF2 binding, suppressing TRAF2 degradation and TNFα-induced cell death. Co-immunoprecipitation (mutant SOD1–KARS1–AIMP2 complex), TRAF2 degradation assay, ALS mouse model (motor neuron function), DX2 overexpression rescue, AAV-DX2 intrathecal injection Molecular neurobiology Medium 36242734
2023 HK2 forms a complex with AIMP2 and promotes its autophagic lysosomal-dependent degradation, thereby attenuating ionizing radiation-mediated apoptosis and conferring radio-resistance in hepatocellular carcinoma cells. Co-immunoprecipitation (HK2–AIMP2), autophagy inhibition assay, HK2 knockdown with apoptosis readout, xenograft model Cell death & disease Medium 37524692
2024 AIMP2-DX2 binds to PARP1 with higher affinity than full-length AIMP2, inhibiting PARP1-induced neuronal cell death (parthanatos) rather than activating it. DX2 translocates to the nucleus more rapidly than full-length AIMP2 under ROS stress. In vivo, AAV-mediated DX2 expression ameliorates behavioral deficits in 6-OHDA Parkinson's disease mouse models. Co-immunoprecipitation (AIMP2 vs. DX2 binding to PARP1), nuclear translocation imaging, PARP1 activation assay, in vivo AAV injection and behavioral assessment Acta neuropathologica communications Medium 38172953
2024 AIMP2 restricts EV71 replication by binding to the viral 3D polymerase (RdRp) and recruiting the E3 ligase SMURF2, which mediates polyubiquitination and degradation of the 3D polymerase. Co-immunoprecipitation (AIMP2–3D polymerase, AIMP2–SMURF2), ubiquitination assay, viral replication assay, knockdown/overexpression Virologica Sinica Medium 38945214
2009 JTV1/AIMP2 physically interacts with NLS-RARα (nuclear localization signal-containing retinoic acid receptor alpha) as shown by yeast two-hybrid and co-immunoprecipitation in HEK293 cells. Yeast two-hybrid, co-immunoprecipitation Sichuan da xue xue bao. Yi xue ban Low 19626986

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience 200 16135753
2013 Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss. Nature neuroscience 184 23974709
2011 JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. The EMBO journal 117 21285945
2008 AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53. Proceedings of the National Academy of Sciences of the United States of America 103 18695251
2011 Cancer-associated splicing variant of tumor suppressor AIMP2/p38: pathological implication in tumorigenesis. PLoS genetics 81 21483803
2009 AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2. Journal of cell science 69 19584093
2019 Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development. Nature chemical biology 40 31792442
2014 Interaction of NS2 with AIMP2 facilitates the switch from ubiquitination to SUMOylation of M1 in influenza A virus-infected cells. Journal of virology 40 25320310
2009 Multidirectional tumor-suppressive activity of AIMP2/p38 and the enhanced susceptibility of AIMP2 heterozygous mice to carcinogenesis. Carcinogenesis 35 19622630
2016 AIMP2 Controls Intestinal Stem Cell Compartments and Tumorigenesis by Modulating Wnt/β-Catenin Signaling. Cancer research 34 27262173
2023 Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2. Cell death & disease 33 37524692
2017 Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. Journal of human genetics 30 29215095
2016 Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2. Cancer research 30 27197155
2020 Amyloid-like oligomerization of AIMP2 contributes to α-synuclein interaction and Lewy-like inclusion. Science translational medicine 28 33177178
2023 Pan-cancer Analysis Identifies AIMP2 as a Potential Biomarker for Breast Cancer. Current genomics 23 38235352
2017 VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2. Cell death & disease 22 28383562
2013 Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression. The Biochemical journal 22 23815603
2012 Selective regression of cancer cells expressing a splicing variant of AIMP2 through targeted RNA replacement by trans-splicing ribozyme. Journal of biotechnology 21 22285955
2019 Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex. The Journal of biological chemistry 20 30733335
2020 Synthesis and Structure-Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy. Journal of medicinal chemistry 19 32315177
2017 Ratio of Autoantibodies of Tumor Suppressor AIMP2 and Its Oncogenic Variant Is Associated with Clinical Outcome in Lung Cancer. Journal of Cancer 18 28638448
2020 Anticancer Activity of Pyrimethamine via Ubiquitin Mediated Degradation of AIMP2-DX2. Molecules (Basel, Switzerland) 17 32549310
2012 Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake. Molecules and cells 15 22562359
2019 The DRS-AIMP2-EPRS subcomplex acts as a pivot in the multi-tRNA synthetase complex. IUCrJ 14 31576228
2013 Rapid detection of exon 2-deleted AIMP2 mutation as a potential biomarker for lung cancer by molecular beacons. Biosensors & bioelectronics 13 23537880
2013 Lentivirus-AIMP2-DX2 shRNA suppresses cell proliferation by regulating Akt1 signaling pathway in the lungs of AIMP2⁺/⁻ mice. Journal of aerosol medicine and pulmonary drug delivery 12 23517169
2022 AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis. Nature communications 11 35546148
2024 Bi-directional regulation of AIMP2 and its splice variant on PARP-1-dependent neuronal cell death; Therapeutic implication for Parkinson's disease. Acta neuropathologica communications 10 38172953
2021 Lewy body-associated proteins: victims, instigators, or innocent bystanders? The case of AIMP2 and alpha-synuclein. Neurobiology of disease 9 34102275
2021 Knockdown of Golgi Stress-Responsive Caspase-2 Ameliorates HLD17-Associated AIMP2 Mutant-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation. Neurochemical research 8 34523057
2018 AIMP2-DX2 Promotes the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells. BioMed research international 8 29854811
2022 Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders. Frontiers in genetics 6 35140751
2022 Pharmacological inhibition of AIMP2 aggregation attenuates α-synuclein aggregation and toxicity in Parkinson's disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 6 36283223
2020 2-Aminophenylpyrimidines as Novel Inhibitors of Aminoacyl-tRNA Synthetase Interacting Multifunctional Protein 2 (AIMP2)-DX2 for Lung Cancer Treatment. Journal of medicinal chemistry 6 32208684
2021 Comparative proteomic profiling reveals a pathogenic role for the O-GlcNAcylated AIMP2-PARP1 complex in aging-related hepatic steatosis in mice. FEBS letters 5 34817071
2017 Purification and biophysical characterization of the AIMP2-DX2 protein. Protein expression and purification 5 28185908
2022 Discovery of benzodioxane analogues as lead candidates of AIMP2-DX2 inhibitors. Bioorganic & medicinal chemistry letters 4 35842206
2022 Anti-apoptotic Splicing Variant of AIMP2 Recover Mutant SOD1-Induced Neuronal Cell Death. Molecular neurobiology 4 36242734
2018 Label-free molecular probe based on G-quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2. Chemical biology & drug design 4 30345633
2024 AIMP2 accumulation in brain leads to cognitive deficits and blood secretion in Parkinson's disease. Journal of translational medicine 3 39390613
2024 Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination. Cell chemical biology 2 39260366
2024 AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase. Virologica Sinica 1 38945214
2024 Assessment the Efficacy of the CRISPR System for Inducing Mutations in the AIMP2 Gene to Create a Cell Line Model of HLD17 Disease. Molecular biotechnology 1 39433694
2024 An extensive in silico analysis of missense mutations of the human AIMP2 gene. Heliyon 1 39640834
2020 Structural insight into the interaction between p53 TAD1 and AIMP2-DX2 by NMR. Biochemical and biophysical research communications 1 32448505
2020 An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody. Biomolecules 1 32471182
2009 [Identification of the interactions between JTV1 and NLS-RAR alpha in vivo and in vitro]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 1 19626986
2024 Identification and structure of AIMP2-DX2 for therapeutic perspectives. BMB reports 0 38835119
2017 Data on optimization of expression and purification of AIMP2-DX2 protein in Escherichia coli. Data in brief 0 28367482

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