Affinage

TRIM32

E3 ubiquitin-protein ligase TRIM32 · UniProt Q13049

Length
653 aa
Mass
72.0 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM32 is a RING-domain E3 ubiquitin ligase that couples substrate ubiquitination to control of cell fate, muscle and neural homeostasis, innate immunity, and tumor suppression (PMID:19349376, PMID:19269368, PMID:22745133). Its catalytic activity drives K48-linked ubiquitination and proteasomal degradation of a broad substrate set — dysbindin at the muscle Z-line (PMID:19349376), c-Myc and MYCN to bias neural progenitors toward differentiation and asymmetric division (PMID:19269368, PMID:25100564), and the tumor-relevant substrates p53, TAp73, ARID1A, NDRG2, and STIM1 (PMID:25146927, PMID:23828567, PMID:31914402, PMID:25701873, PMID:37542345); for several of these it sits in regulatory loops, being a transcriptional target of p53 and TAp73 while degrading them (PMID:25146927, PMID:23828567). In innate immunity it functions both catalytically — K63-ubiquitinating STING/MITA to enhance IFN-β induction and ubiquitinating influenza PB1 polymerase to restrict viral replication (PMID:22745133, PMID:26057645) — and non-catalytically, bridging TRIF to TAX1BP1 for selective autophagic degradation to dampen TLR signaling (PMID:28898289). TRIM32 is a central activator of autophagy: it generates K63-linked unanchored polyubiquitin chains that activate ULK1 within an AMBRA1–ULK1 complex, mono-ubiquitylates p62/SQSTM1, and ubiquitinates ATG7 downstream of ATM–CHK2 phosphorylation at Ser55 (PMID:31234693, PMID:31685529, PMID:37943659), and promotes xenophagic clearance of Mycobacterium tuberculosis (PMID:37543647). In skeletal muscle it additionally suppresses PI3K-Akt-FoxO growth signaling by displacing plakoglobin from p85 (PMID:24567360). Loss-of-function NHL-domain mutations (D487N, R394H) that impair self-interaction, E2 binding, and substrate ubiquitination cause limb-girdle muscular dystrophy type 2H, while a distinct B-box mutation (P130S) causes Bardet-Biedl syndrome type 11 (PMID:11822024, PMID:16606853, PMID:17994549, PMID:19349376).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 Medium

    Established TRIM32 as a disease gene by linking an NHL-domain mutation to limb-girdle muscular dystrophy, raising the question of how a RING-containing protein causes myopathy.

    Evidence Genetic mapping and candidate-gene sequencing in affected families

    PMID:11822024

    Open questions at the time
    • E3 ligase activity only inferred from RING domain, not demonstrated
    • No substrate identified
    • Muscle-specific mechanism unknown
  2. 2003 Medium

    Demonstrated TRIM32 is a bona fide E3 ligase capable of auto-ubiquitylation, moving the field from domain inference to biochemical activity and an anti-apoptotic cellular role.

    Evidence In vitro ubiquitylation assays and apoptosis assays in keratinocytes

    PMID:14578165

    Open questions at the time
    • No physiological substrate defined
    • Anti-apoptotic mechanism not connected to specific targets
  3. 2006 Medium

    Showed a separate B-box mutation causes Bardet-Biedl syndrome, establishing that distinct TRIM32 domains drive mechanistically distinct diseases.

    Evidence Homozygosity mapping, mutation analysis, zebrafish validation

    PMID:16606853

    Open questions at the time
    • Ciliary mechanism not defined at the time
    • Why B-box vs NHL mutations give different diseases unexplained
  4. 2008 Medium

    Resolved how NHL-domain LGMD2H mutations act, showing they impair self-interaction, E2 binding, and localization while the BBS B-box mutant does not, explaining domain-specific pathomechanisms.

    Evidence Yeast two-hybrid, co-IP, and localization of disease mutants

    PMID:17994549

    Open questions at the time
    • Did not identify the muscle substrate whose loss causes disease
    • In vitro interaction data only
  5. 2009 High

    Identified the first physiological substrates and processes: dysbindin degradation at the muscle Z-line and c-Myc degradation during asymmetric neural progenitor division, linking TRIM32 to both muscle and neural fate control.

    Evidence In vitro ubiquitination, Y2H, Co-IP, siRNA, KO mouse, imaging (multiple studies)

    PMID:19155210 PMID:19269368 PMID:19349376

    Open questions at the time
    • Direct K-linkage chains on dysbindin not fully defined
    • How polarization is achieved mechanistically unresolved
    • Relative contribution of neural vs muscle defects to disease unclear
  6. 2011 Medium

    Extended TRIM32 function to transcription-factor regulation and clarified that loss of protein stability underlies the LGMD2H knock-in phenotype.

    Evidence Co-IP and transcriptional assays for RARα; knock-in mouse mRNA/protein comparison

    PMID:21775502 PMID:21984809

    Open questions at the time
    • RARα stabilization mechanism (catalytic vs non-catalytic) not resolved
    • Whether D489N is a true null in all tissues unconfirmed
  7. 2012 High

    Defined TRIM32 as an antiviral signaling amplifier (K63-ubiquitination of STING/MITA) and confirmed its c-Myc-dependent role in satellite-cell myogenesis, broadening it across immunity and muscle regeneration.

    Evidence Ubiquitination with site mutagenesis, fractionation, antiviral assays; KO mouse myogenesis assays

    PMID:22299041 PMID:22745133

    Open questions at the time
    • How a Z-line/cytosolic ligase accesses mitochondrial/ER STING not fully explained
    • Direct vs indirect c-Myc regulation in muscle
  8. 2012 High

    Demonstrated through the Drosophila ortholog Thin that TRIM32 maintains myofibril integrity via costamere stability, providing a structural rationale for the dystrophic phenotype.

    Evidence Loss-of-function, rescue, and costameric protein staining in Drosophila

    PMID:23071324

    Open questions at the time
    • Whether costamere maintenance is ubiquitination-dependent unknown
    • Direct substrate among costameric proteins not identified
  9. 2013 Medium

    Embedded TRIM32 in p73 and adult-neurogenesis circuits, showing it degrades TAp73 in a feedback loop and is required for proper neuronal differentiation versus progenitor expansion.

    Evidence ChIP, reporter, Co-IP, ubiquitination assays; KO mouse neurogenesis analysis

    PMID:23828567 PMID:24357807

    Open questions at the time
    • Ubiquitin chain type on TAp73 not defined
    • Mechanism distinguishing self-renewal vs differentiation outputs incomplete
  10. 2014 High

    Established TRIM32 as a tumor-suppressor antagonist and asymmetric-division regulator: it degrades p53 (in a p53-induced feedback loop) and MYCN at spindle poles after CDK1/cyclin B recruitment, and suppresses muscle PI3K-Akt-FoxO signaling.

    Evidence ChIP, Co-IP, ubiquitination, kinase assay, atrophy/tumor models (multiple studies)

    PMID:24567360 PMID:25100564 PMID:25146927

    Open questions at the time
    • How TRIM32 toggles between pro-survival (p53 degradation) and pro-apoptotic roles unresolved
    • Spindle-pole recruitment determinants beyond CDK1 phosphorylation incomplete
  11. 2015 High

    Identified additional muscle and antiviral substrates (NDRG2 in myoblast proliferation; influenza PB1 as a restriction target), confirming catalytic activity is required for viral restriction.

    Evidence 2D-DIGE, in vitro ubiquitination, KO tissue Western; AP-MS, KO/reconstitution, catalytic mutant viral assays

    PMID:25701873 PMID:26057645

    Open questions at the time
    • NDRG2 chain linkage not defined
    • How TRIM32 traffics to the nucleus with PB1 mechanistically unclear
  12. 2017 High

    Revealed TRIM32 acts non-catalytically as an adaptor bridging TRIF to TAX1BP1 for selective autophagy, and extended substrate degradation roles to cardiomyocytes and to cell-cycle-coupled ciliogenesis via NPHP5.

    Evidence Co-IP, autophagy/TAX1BP1 KO, KO mouse infection; cardiomyocyte assays; centrosome ubiquitination/ciliogenesis assays

    PMID:28465353 PMID:28498859 PMID:28898289

    Open questions at the time
    • Switch between catalytic and adaptor modes not defined
    • Connection between NPHP5 ciliary mechanism and BBS B-box mutation unclear
  13. 2019 High

    Positioned TRIM32 as a direct autophagy initiator, generating unanchored K63 chains to activate ULK1 in the AMBRA1 complex and mono-ubiquitylating p62, with LGMD2H mutants failing both functions.

    Evidence ULK1 kinase activity reconstitution, ubiquitination, Co-IP, autophagy flux, disease-mutant analysis (two studies)

    PMID:31234693 PMID:31685529

    Open questions at the time
    • How unanchored chains are assembled and delivered to ULK1 not detailed
    • Relative importance of autophagy vs proteasomal substrates to LGMD2H unresolved
  14. 2020 Medium

    Broadened TRIM32 substrate scope into mTOR signaling (RGS10 degradation, GABAergic neuron generation), SCC oncogenesis (ARID1A degradation), glycolysis, and oxidative-stress apoptosis.

    Evidence KO mouse with rescue, Co-IP/ubiquitination, tumor models, Drosophila metabolomics, ROS/XIAP assays (multiple studies)

    PMID:31828304 PMID:31914402 PMID:32223900 PMID:32918979

    Open questions at the time
    • Whether glycolytic-enzyme interaction is ubiquitination-dependent unknown
    • Tissue-specific selection among the many substrates not explained
  15. 2023 High

    Defined upstream regulation of TRIM32 by ATM–CHK2 phosphorylation at Ser55 driving ATG7 K63-ubiquitination, added STIM1/calcium and tuberculosis xenophagy roles, integrating stress signaling with TRIM32-driven autophagy.

    Evidence Kinase and ubiquitination assays with site mutagenesis, KO mouse stroke model; Co-IP/competition assays; macrophage Mtb assays

    PMID:37542345 PMID:37543647 PMID:37943659

    Open questions at the time
    • Whether Ser55 phosphorylation gates other substrates unknown
    • How TRIM32 selects targets across stress contexts unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ligase selects among its many substrates and switches between K48/K63/mono-ubiquitination and catalytic versus adaptor modes in a tissue- and stress-specific manner remains unresolved.
  • No structural model of NHL substrate recognition across targets
  • Determinants of chain-linkage choice undefined
  • Mechanism connecting BBS B-box vs LGMD2H NHL mutations to distinct phenotypes incompletely understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016874 ligase activity 6 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005739 mitochondrion 2 GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-397014 Muscle contraction 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2
Partners
AMBRA1DTNBP1P53SQSTM1STING1TP73TRIFULK1
Complex memberships
AMBRA1-ULK1 autophagy initiation complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TRIM32 (D487N mutation) was identified as causative for limb-girdle muscular dystrophy type 2H (LGMD2H); the mutation occurs in the NHL domain at a position highly conserved and involved in protein-protein interactions, consistent with TRIM32 functioning as an E3 ubiquitin ligase based on its RING domain. Genetic mapping, sequencing of candidate genes, homozygosity testing in affected families and controls American journal of human genetics Medium 11822024
2003 TRIM32 exhibits E3 ubiquitin ligase properties including auto-ubiquitylation and interaction with ubiquitylated proteins; it inhibits TNF-α/UVB-induced apoptosis in keratinocytes, suggesting its ligase activity promotes cell survival by blocking apoptotic signaling. Ubiquitylation assays, in vitro transformation assay, in vivo skin graft, apoptosis assays Carcinogenesis Medium 14578165
2006 A missense mutation in the B-box domain of TRIM32 (P130S) causes Bardet-Biedl syndrome type 11 (BBS11), identifying TRIM32 as a BBS gene and implicating the proteasome/ubiquitin degradation pathway in BBS pathogenesis. SNP microarray homozygosity mapping, mutation analysis, zebrafish functional analysis, expression quantitative trait loci analysis Proceedings of the National Academy of Sciences of the United States of America Medium 16606853
2008 LGMD2H-associated TRIM32 mutations (D487N, R394H) cluster in NHL domains, impair TRIM32 self-interaction and interaction with the E2 enzyme, and are mislocalized in cells; the BBS11 mutant (P130S) does not show these biochemical defects. This indicates NHL domain mutations cause disease through loss of protein-protein interaction capacity. Yeast two-hybrid interaction assay, co-immunoprecipitation, subcellular localization in transfected cells Human mutation Medium 17994549
2009 TRIM32 ubiquitinates and degrades dysbindin (DTNBP1) via its E3 ligase activity; LGMD2H/STM mutations D487N and R394H impair ubiquitin ligase activity toward dysbindin. TRIM32 is localized to the Z-line in skeletal muscle. siRNA knockdown of TRIM32 in myoblasts elevates dysbindin levels. Yeast two-hybrid, in vitro ubiquitination assay, co-immunoprecipitation, siRNA knockdown, immunofluorescence localization Human molecular genetics High 19349376
2009 TRIM32 is polarized during mitosis in mouse neural progenitors and becomes concentrated in one daughter cell. It ubiquitinates and degrades c-Myc and binds Argonaute-1 to increase activity of specific microRNAs (including Let-7), thereby promoting neuronal differentiation over progenitor self-renewal. Immunostaining and live imaging for polarization, ubiquitination assay for c-Myc, co-immunoprecipitation with Argonaute-1, microRNA activity assays, overexpression and inhibition experiments Cell High 19269368
2009 Trim32 knockout mice develop a myopathy with neurogenic features: histological myopathic changes, Z-line streaming, dilated sarcotubular system; additionally decreased neurofilament concentration and reduced myelinated motor axon diameters. TRIM32 is expressed at much higher levels in brain than skeletal muscle. Knockout mouse generation, histology, electron microscopy, real-time PCR, neurofilament analysis Human molecular genetics High 19155210
2011 TRIM32 interacts with retinoic acid receptor α (RARα) and enhances its transcriptional activity in the presence of retinoic acid; TRIM32 overexpression promotes stability of RARα and enhances neural differentiation in neuroblastoma and embryonal carcinoma cells. Co-immunoprecipitation, transcriptional activity assays, overexpression in cell lines, differentiation assays Journal of cell science Medium 21984809
2011 The common LGMD2H-associated D489N mutation in mouse Trim32 leads to loss of the mutant protein at the protein level (normal mRNA but severe reduction in protein), suggesting that the pathogenic mutation destabilizes TRIM32 and results in a null phenotype, explaining why knock-in mice phenocopy Trim32-null mice. Knock-in mouse generation, quantitative RT-PCR, Western blot Human molecular genetics Medium 21775502
2012 TRIM32 ubiquitinates MITA/STING at K20/150/224/236 with K63-linked chains through its E3 ubiquitin ligase activity, promoting MITA-TBK1 interaction and downstream IRF3 activation to enhance IFN-β induction and cellular antiviral response. TRIM32 localizes to mitochondria and endoplasmic reticulum. Co-immunoprecipitation, ubiquitination assay, mutagenesis of ubiquitination sites, overexpression/knockdown, subcellular fractionation/localization, antiviral response assays The Journal of biological chemistry High 22745133
2012 TRIM32 regulates skeletal muscle satellite cell differentiation; loss of TRIM32 impairs myogenic differentiation via dysregulation of c-Myc, causing a LGMD2H-like phenotype and defective muscle regeneration in vivo. Knockout mouse analysis, myoblast differentiation assays, c-Myc protein level analysis, in vivo muscle regeneration after injury PloS one Medium 22299041
2012 Drosophila Thin (tn), the TRIM32 ortholog, is localized at the Z-disk in muscle and is required for costamere integrity; tn mutants show progressive disorganization of costameric proteins (β-integrin, Spectrin, Talin, Vinculin) and myofibril unbundling, demonstrating TRIM32's role in myofibril stability via costamere maintenance. Loss-of-function and rescue experiments in Drosophila, immunostaining for costameric proteins, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 23071324
2013 TRIM32 is a direct transcriptional target of TAp73; TRIM32 physically interacts with TAp73 and promotes its ubiquitination and degradation, thereby impairing p73-dependent transcriptional activity. DNp73 represses TRIM32 expression, forming a negative feedback loop between p73 and TRIM32 in neural progenitor cells. Chromatin immunoprecipitation, reporter assays, co-immunoprecipitation, ubiquitination assays Cell death & disease Medium 23828567
2013 TRIM32 is upregulated during differentiation of adult neural stem cells; TRIM32 deficiency impairs neuronal differentiation, increases progenitor proliferation, reduces cell death, and results in overproduction of adult-generated olfactory bulb neurons in TRIM32 KO mice. KO mouse analysis, BrdU labeling, gene expression profiling, behavioral assays Cell death & disease Medium 24357807
2014 TRIM32 is a p53 target gene; p53 binds the TRIM32 promoter and induces TRIM32 expression in response to DNA damage stress; TRIM32 in turn interacts with p53 and promotes its ubiquitination and degradation, negatively regulating p53-mediated apoptosis, cell cycle arrest, and senescence. ChIP assay, reporter assay, co-immunoprecipitation, ubiquitination assay, apoptosis/senescence assays, mouse tumor models Cell death and differentiation High 25146927
2014 Trim32 ubiquitinates and degrades MYCN at spindle poles during mitosis. TRIM32 is recruited to spindle poles by CDK1/cyclin B-mediated phosphorylation and interacts with MYCN there, facilitating asymmetric cell division in human neuroblastoma cells. Co-immunoprecipitation, ubiquitination assay, immunofluorescence/localization, kinase assay (CDK1/cyclin B phosphorylation), sphere formation assay Cancer research Medium 25100564
2014 Trim32 suppresses PI3K-Akt-FoxO signaling in muscle atrophy by promoting dissociation of plakoglobin from PI3K subunit p85; inhibition of Trim32 enhances plakoglobin-PI3K-p85 binding and activates PI3K-Akt-FoxO signaling, increasing glucose uptake and inducing fiber growth. Co-immunoprecipitation, knockdown/overexpression in muscle, glucose uptake assay, atrophy model The Journal of cell biology High 24567360
2015 TRIM32 acts as an intrinsic restriction factor against influenza A virus by directly interacting with and ubiquitinating PB1 polymerase, leading to PB1 protein degradation and reduced polymerase activity. TRIM32 translocates with PB1 to the nucleus upon IAV infection. Catalytically inactive TRIM32 fails to restrict viral replication. Affinity purification/mass spectrometry, co-immunoprecipitation, ubiquitination assay, KO/reconstitution in MEFs, RNAi in epithelial cells, catalytic mutant analysis, viral replication assays PLoS pathogens High 26057645
2015 TRIM32 ubiquitinates NDRG2 in vitro and in skeletal muscle; NDRG2 accumulates in TRIM32-KO muscle and myoblasts; NDRG2 overexpression reduces myoblast proliferation. TRIM72 was also identified as a TRIM32 substrate in vitro but did not accumulate significantly in vivo. 2D fluorescence difference gel electrophoresis (2D-DIGE), in vitro ubiquitination assay, Western blot in KO tissue, overexpression proliferation assays Human molecular genetics Medium 25701873
2017 TRIM32 negatively regulates TLR3/4-mediated innate immune responses by targeting the adaptor protein TRIF for TAX1BP1-mediated selective autophagic degradation in an E3-ligase-activity-independent manner. TRIM32 links TRIF and TAX1BP1 through distinct domains. Trim32-/- mice are hypersensitive to Salmonella infection. Co-immunoprecipitation, selective autophagy inhibitor/TAX1BP1 KO studies, KO mice infection model, cytokine measurements PLoS pathogens High 28898289
2017 TRIM32 ubiquitinates and degrades dysbindin in neonatal rat ventricular cardiomyocytes, suppressing dysbindin-induced SRF signaling and hypertrophy. TRIM32 also activates p53 and caspase-3/-7 and inhibits XIAP in cardiomyocytes, regulating cardiomyocyte viability and apoptosis. Co-immunoprecipitation, Western blot for SRF pathway, hypertrophy assays, apoptosis assays (caspase activity), overexpression/knockdown The Journal of biological chemistry Medium 28465353
2017 TRIM32 (BBS11) K63-ubiquitinates NPHP5 at the centrosome during G2/M phase to trigger NPHP5 delocalization and cilia loss. USP9X deubiquitinates NPHP5 in G0/G1/S to protect cilia assembly. This dynamic ubiquitination/deubiquitination cycle coordinates ciliogenesis with the cell cycle. Co-immunoprecipitation, ubiquitination assays, centrosome localization studies, cell cycle synchronization, siRNA knockdown, ciliogenesis assays PLoS genetics Medium 28498859
2019 TRIM32 mono-ubiquitylates p62/SQSTM1 on lysine residues to facilitate p62 sequestration and autophagic degradation. p62 reciprocally directs TRIM32 for lysosomal degradation by selective autophagy. The LGMD2H disease mutant of TRIM32 cannot undergo autophagic degradation and fails to mono-ubiquitylate p62. Knockout cell lines, co-immunoprecipitation, ubiquitination assays, autophagy flux assays, reintroduction of WT vs. mutant TRIM32 Journal of cell science High 31685529
2019 TRIM32 forms a complex with AMBRA1 and ULK1; TRIM32 activates ULK1 kinase activity through K63-linked unanchored polyubiquitin chains, thereby initiating autophagy in muscle cells upon atrophy induction. LGMD2H mutations in TRIM32 disrupt binding to ULK1 and fail to induce autophagy. Co-immunoprecipitation, ubiquitination assays, ULK1 kinase activity assay, autophagy flux assays, disease mutant analysis Autophagy High 31234693
2020 TRIM32 maintains mTOR activity by promoting proteasomal degradation of RGS10, a GTPase-activating protein; TRIM32 deficiency reduces mTOR activity, impairs generation of GABAergic interneurons from medial/lateral ganglionic eminence progenitors, and leads to autism-like behaviors in mice. Treatment with mTOR activator 3BDO rescues these defects. KO mouse, co-immunoprecipitation/pulldown, proteasome inhibitor experiments, electrophysiology, behavioral assays, cell transplantation rescue Cerebral cortex Medium 31828304
2020 TRIM32 ubiquitinates ARID1A to promote its proteasomal degradation in squamous cell carcinoma; USP11 deubiquitinase counteracts TRIM32 to stabilize ARID1A. TRIM32 depletion inhibits SCC proliferation, metastasis, and chemoresistance by stabilizing ARID1A, acting through the downstream target SDC2. Co-immunoprecipitation, ubiquitination assay, TRIM32 KD/OE, in vitro and in vivo tumor models, Western blot Cell reports Medium 31914402
2020 Drosophila TRIM32 (Thin) physically interacts with glycolytic enzymes Aldolase and Phosphoglycerate mutase; loss of TRIM32 reduces glycolytic intermediates and amino acids, resulting in reduced muscle and brain tissue size. TRIM32 is required for glycolytic flux and ectopic tumor growth. Biochemical interaction assays (co-IP/pulldown), metabolomics in tn mutants, tissue size measurements, dietary supplementation rescue, tumor model eLife Medium 32223900
2020 TRIM32 regulates mitochondrial ROS levels and sensitizes cells to oxidative stress-induced apoptosis; TRIM32 expression reduces XIAP levels and its E3 ligase activity is required for this pro-apoptotic effect. TRIM32 forms cytoplasmic speckles that transiently interact with mitochondria under oxidative stress. Overexpression/knockdown, ROS measurement, mitochondrial membrane potential assay, complex-I activity assay, co-localization imaging, XIAP overexpression rescue Cellular signalling Medium 32918979
2023 TRIM32 ubiquitinates STIM1 to promote its degradation; TSPAN18 competitively inhibits TRIM32-mediated STIM1 ubiquitination by binding STIM1, stabilizing STIM1 protein and enhancing store-operated calcium entry. Co-immunoprecipitation, ubiquitination assay, liquid chromatography-mass spectrometry, in vitro and in vivo cancer models Journal of experimental & clinical cancer research Medium 37542345
2023 CHK2 phosphorylates TRIM32 at S55 downstream of ATM (activated by ROS); phosphorylated TRIM32 then mediates K63-linked ubiquitination of ATG7 at K45 to initiate autophagy. Chk2-/- mice show reduced TRIM32 phosphorylation and reduced ATG7 ubiquitination in a stroke model. Co-immunoprecipitation, kinase assay, ubiquitination assay with site mutagenesis, KO mouse stroke model, phosphorylation site identification Cell reports High 37943659
2023 TRIM32 promotes autophagy-mediated (xenophagy) degradation of Mycobacterium tuberculosis in macrophages; TRIM32 knockdown impairs Mtb ubiquitination, reduces recruitment of autophagy receptors NDP52 and BECLIN1, and increases intracellular Mtb growth. TRIM32 ectopic expression/knockdown in THP1 macrophages, Mtb replication assay, immunofluorescence for autophagy receptors, ubiquitination assay Cell death & disease Medium 37543647

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. Journal of psychiatry & neuroscience : JPN 367 15309042
2012 TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination. The Journal of biological chemistry 345 22745133
2009 The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 335 19269368
2006 Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11). Proceedings of the National Academy of Sciences of the United States of America 294 16606853
2015 The role of serotonin 5-HT2A receptors in memory and cognition. Frontiers in pharmacology 272 26500553
2002 Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 210 12589395
2002 Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. American journal of human genetics 201 11822024
1995 The role of 5-HT2A receptors in antipsychotic activity. Life sciences 191 7791509
2003 5-HT2A and 5-HT2C receptors and their atypical regulation properties. Life sciences 176 12650852
2013 Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo. PloS one 166 24098382
2004 Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacology & therapeutics 155 15500909
2015 TRIM32 Senses and Restricts Influenza A Virus by Ubiquitination of PB1 Polymerase. PLoS pathogens 140 26057645
1997 Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway. The Journal of biological chemistry 133 9169451
2014 E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis. Cell death and differentiation 126 25146927
2009 TRIM32 is an E3 ubiquitin ligase for dysbindin. Human molecular genetics 112 19349376
2003 RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties. Carcinogenesis 107 14578165
2017 TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. PLoS pathogens 106 28898289
2014 Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists. ACS chemical neuroscience 100 24397362
2015 Central serotonin-2A (5-HT2A) receptor dysfunction in depression and epilepsy: the missing link? Frontiers in pharmacology 97 25852551
2009 Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Human molecular genetics 96 19155210
2008 Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors. Pharmacology & therapeutics 94 19109993
1998 Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation. Critical reviews in neurobiology 90 10348614
2005 Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors. Trends in pharmacological sciences 88 16269190
2000 Pontomedullary distribution of 5-HT2A receptor-like protein in the rat. The Journal of comparative neurology 88 10701830
2011 Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 87 21645528
2014 Trim32 reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. The Journal of cell biology 80 24567360
2008 Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Human mutation 78 17994549
2016 The 5-HT2A serotonin receptor in executive function: Implications for neuropsychiatric and neurodegenerative diseases. Neuroscience and biobehavioral reviews 75 26891819
2005 Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. Annals of neurology 73 15786463
2003 Increased coronary events in depressed cardiovascular patients: 5-HT2A receptor as missing link? Psychosomatic medicine 69 14508013
1996 Regulation of central 5-HT2A receptors: a review of in vivo studies. Behavioural brain research 69 8788498
2012 TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration. PloS one 65 22299041
2015 5-HT2A receptor activation is necessary for CO2-induced arousal. Journal of neurophysiology 59 25925320
2016 Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures. Neuropharmacology 57 27085605
2016 TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours. The international journal of biochemistry & cell biology 57 27458054
1998 Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists. Annals of the New York Academy of Sciences 56 9928246
1995 Repeated ECS differentially affects rat brain 5-HT1A and 5-HT2A receptor expression. Neuroreport 56 7612879
2002 5-HT2A receptor gene promoter polymorphism in relation to abdominal obesity and cortisol. Obesity research 55 12105278
2006 Involvement of a polymorphism in the 5-HT2A receptor gene in impulsive behavior. Psychopharmacology 53 16767413
2005 Expression of the 5-HT2A serotoninergic receptor in human placenta and choriocarcinoma cells: mitogenic implications of serotonin. Placenta 53 15950062
2011 TRIM32 promotes neural differentiation through retinoic acid receptor-mediated transcription. Journal of cell science 51 21984809
2018 TRIM32 promotes cell proliferation and invasion by activating β-catenin signalling in gastric cancer. Journal of cellular and molecular medicine 50 30079558
2001 5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder. Psychiatric genetics 50 11702051
1998 Activation of the mitogen-activated protein kinase pathway via the 5-HT2A receptor. Annals of the New York Academy of Sciences 50 9928253
2019 Sustained Activation of Postsynaptic 5-HT2A Receptors Gates Plasticity at Prefrontal Cortex Synapses. Cerebral cortex (New York, N.Y. : 1991) 48 29917056
2014 Trim32 facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. Cancer research 48 25100564
2013 Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions. Experimental brain research 48 23591691
2005 Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907. Synapse (New York, N.Y.) 48 16206185
1998 5-HT2A receptor antagonists block MK-801-induced stereotypy and hyperlocomotion. European journal of pharmacology 48 9808259
2020 TRIM32/USP11 Balances ARID1A Stability and the Oncogenic/Tumor-Suppressive Status of Squamous Cell Carcinoma. Cell reports 47 31914402
2018 TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. Journal of Cancer 47 29721043
2004 5-HT2A T102C receptor polymorphism and neuropsychiatric symptoms in Alzheimer's disease. International journal of geriatric psychiatry 47 15211529
2013 5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis. Liver international : official journal of the International Association for the Study of the Liver 44 23362947
2012 Functional selectivity in serotonin receptor 2A (5-HT2A) endocytosis, recycling, and phosphorylation. Molecular pharmacology 41 23034456
2017 TRIM24 protein promotes and TRIM32 protein inhibits cardiomyocyte hypertrophy via regulation of dysbindin protein levels. The Journal of biological chemistry 39 28465353
2010 Role of 5-HT2A receptor antagonists in the treatment of insomnia. Nature and science of sleep 39 23616706
2020 Absence of TRIM32 Leads to Reduced GABAergic Interneuron Generation and Autism-like Behaviors in Mice via Suppressing mTOR Signaling. Cerebral cortex (New York, N.Y. : 1991) 38 31828304
2015 The E3 ubiquitin ligase TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2. Human molecular genetics 38 25701873
2014 The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function. PloS one 38 24466319
2012 Thin, a Trim32 ortholog, is essential for myofibril stability and is required for the integrity of the costamere in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 38 23071324
2016 Fish TRIM32 functions as a critical antiviral molecule against iridovirus and nodavirus. Fish & shellfish immunology 37 27847343
2011 Limb-girdle muscular dystrophy 2H and the role of TRIM32. Handbook of clinical neurology 37 21496629
2011 The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype. Human molecular genetics 37 21775502
2002 5-HT2A receptor activation leads to increased BDNF mRNA expression in C6 glioma cells. Neuromolecular medicine 37 12095161
1996 Intact 5-HT2A receptor exons and the adjoining intron regions in schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 37 8703302
2020 TRIM32 Promotes the Growth of Gastric Cancer Cells through Enhancing AKT Activity and Glucose Transportation. BioMed research international 36 32051827
2015 SseK3 Is a Salmonella Effector That Binds TRIM32 and Modulates the Host's NF-κB Signalling Activity. PloS one 36 26394407
2013 TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation. Cell death & disease 36 24357807
2018 Expression and the potential functions of TRIM32 in lung cancer tumorigenesis. Journal of cellular biochemistry 35 30378152
2017 USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to regulate ciliogenesis. PLoS genetics 35 28498859
2020 Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth. eLife 34 32223900
2016 Effect of 5-HT2A and 5-HT2C receptors on temporal discrimination by mice. Neuropharmacology 34 27020041
2011 Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice. Psychopharmacology 32 21340474
2007 Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach. BMC psychiatry 32 17521439
2011 Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors. Physiology & behavior 31 21362435
2014 Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress. The European journal of neuroscience 30 24839933
2013 Regulatory feedback loop between TP73 and TRIM32. Cell death & disease 30 23828567
2009 Use of SNP array analysis to identify a novel TRIM32 mutation in limb-girdle muscular dystrophy type 2H. Neuromuscular disorders : NMD 30 19303295
2006 ACP-103, a 5-HT2A receptor inverse agonist. Current opinion in investigational drugs (London, England : 2000) 30 16869120
2003 Behavioral evidence for mu-opioid and 5-HT2A receptor interactions. European journal of pharmacology 30 12909198
2023 TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination. Journal of experimental & clinical cancer research : CR 29 37542345
2009 Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H. Human mutation 29 19492423
2023 The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages. Cell death & disease 28 37543647
2021 TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis. Biomolecules 28 33802079
2020 TRIM32 regulates mitochondrial mediated ROS levels and sensitizes the oxidative stress induced cell death. Cellular signalling 28 32918979
2007 5-HT2A SNPs and the Temperament and Character Inventory. Progress in neuro-psychopharmacology & biological psychiatry 28 17590256
2002 5-HT2A antagonists in psychiatric disorders. Current opinion in investigational drugs (London, England : 2000) 28 12054060
2023 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress. Cell reports 27 37943659
2019 A TRIM32-AMBRA1-ULK1 complex initiates the autophagy response in atrophic muscle cells. Autophagy 27 31234693
2019 TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1. Journal of cell science 27 31685529
2020 TRIM32 Deficiency Impairs Synaptic Plasticity by Excitatory-Inhibitory Imbalance via Notch Pathway. Cerebral cortex (New York, N.Y. : 1991) 26 32219328
2019 Altered myogenesis and premature senescence underlie human TRIM32-related myopathy. Acta neuropathologica communications 25 30823891
2016 Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic Dermatitis. The Journal of investigative dermatology 25 27720760
2009 Emotional management and 5-HT2A receptor gene variance in patients with schizophrenia. Biological psychology 25 19913072
2005 Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I. European journal of human genetics : EJHG 25 15886712
2016 5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis. Behavioural pharmacology 24 26292187
2015 Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy. Investigative ophthalmology & visual science 24 26200496
2005 Molecular and pharmacological characterization of serotonin 5-HT2A and 5-HT2B receptor subtypes in dog. European journal of pharmacology 24 15862800
2021 A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear. The international journal of neuropsychopharmacology 23 34228806
2019 Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury. Stem cells (Dayton, Ohio) 22 31621984

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