Affinage

ARIH1

E3 ubiquitin-protein ligase ARIH1 · UniProt Q9Y4X5

Length
557 aa
Mass
64.1 kDa
Annotated
2026-04-28
66 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARIH1 (HHARI) is a RING-between-RING (RBR) E3 ubiquitin ligase that functions as a central effector of CRL-coupled ubiquitination and innate immune signaling. Its RING1 domain recruits the E2 enzyme UbcH7 and uses a unique Zn²⁺-loop II steric wedge to enforce an open E2~Ub conformation, directing ubiquitin transfer through an obligate thioester intermediate on the RING2 catalytic cysteine — a RING/HECT hybrid mechanism capable of forming both lysine isopeptide and serine oxyester bonds on substrates (PMID:21532592, PMID:28552575, PMID:37870100). Auto-inhibited in isolation, ARIH1 is allosterically activated by association with neddylated Cullin-RING ligase complexes, whereupon it ubiquitinates diverse substrates including PD-L1 (primed by GSK3α phosphorylation), DNA-PKcs, 4EHP, cGAS (via ISGylation), HER2, and MFN2, thereby controlling immune checkpoint protein turnover, DNA damage-induced translational arrest, cGAS-STING pathway activation, and mitochondrial dynamics (PMID:24076655, PMID:33879767, PMID:25624349, PMID:36217001, PMID:37429863). ARIH1 also mono-ISGylates cGAS at Lys187 to promote its oligomerization and type I interferon production, and ARIH1 knockout mice show hypersensitivity to HSV-1 and altered autoimmune responses (PMID:36217001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Establishing that ARIH1 is a ubiquitin-pathway E3 that selectively pairs with UbcH7/UbcH8 via its RING-IBR domains answered the question of which E2 enzymes this Ariadne-family protein engages.

    Evidence Yeast two-hybrid and in vitro pulldown assays with domain truncations

    PMID:10521492

    Open questions at the time
    • No catalytic mechanism defined
    • Substrate identity unknown
  2. 2001 High

    Mapping the minimal UbcH7-binding region and demonstrating perinuclear co-localization refined where and how ARIH1 engages its cognate E2 in cells.

    Evidence Co-IP, co-localization by fluorescence microscopy, point mutagenesis in mammalian cells

    PMID:11278816

    Open questions at the time
    • Catalytic transfer mechanism still uncharacterized
    • No substrates identified
  3. 2006 Medium

    Genetic studies in C. elegans established that ARI-1/ARIH1 acts as the principal E3 downstream of UBC-18/UbcH7 in a developmental context (pharyngeal morphogenesis), demonstrating in vivo functional relevance of the E2–E3 pairing.

    Evidence Yeast two-hybrid, genetic epistasis with double mutants in C. elegans

    PMID:16457801

    Open questions at the time
    • Mechanism of ubiquitin transfer still unknown
    • Substrates in pharyngeal development unidentified
    • Single model organism
  4. 2011 High

    The discovery that ARIH1 transfers ubiquitin via an obligate thioester intermediate on its RING2 cysteine — rather than directly from E2 to substrate — fundamentally reclassified RBR ligases as RING/HECT hybrids and resolved the catalytic mechanism.

    Evidence In vitro ubiquitination with active-site cysteine mutagenesis and thioester intermediate trapping

    PMID:21532592

    Open questions at the time
    • Structural basis for E2~Ub conformation not yet resolved
    • Activation mechanism unknown
    • Physiological substrates unidentified
  5. 2012 Medium

    Demonstration that ARIH1 localizes to both nucleus and cytoplasm, co-localizes with Cajal and PML bodies, and that its knockdown causes apoptosis and G2 arrest linked ARIH1 to cell proliferation and nuclear body function.

    Evidence Immunofluorescence co-localization, siRNA knockdown with cell cycle analysis

    PMID:23059369

    Open questions at the time
    • Substrates at nuclear bodies unknown
    • Mechanistic link between ARIH1 and G2 arrest not resolved
    • Single lab
  6. 2013 High

    The finding that neddylated CRL complexes bind and allosterically activate ARIH1 resolved the paradox of ARIH1's auto-inhibition and identified CRL neddylation as the physiological activating signal.

    Evidence In vitro ubiquitylation with neddylated CRLs, activity-based Ub-VME probes, genetic epistasis

    PMID:24076655

    Open questions at the time
    • Structural basis of CRL-mediated activation not defined
    • Substrate scope of activated ARIH1 unknown
  7. 2013 Medium

    NMR structure of the RING2 (Rcat) domain revealed the catalytic cysteine environment and a tandem aromatic pair paralleling HECT domain architecture, providing the structural rationale for hybrid E3 catalysis.

    Evidence NMR structure determination and structural comparison with NEDD4

    PMID:24058416

    Open questions at the time
    • No full-length ARIH1 structure
    • Functional mutagenesis of aromatic residues not performed in this study
  8. 2015 High

    Identification of 4EHP as a non-degradative ARIH1 substrate that mediates DNA damage-induced translational arrest established the first defined physiological function — linking ATM signaling through ARIH1 to cap-dependent translation repression.

    Evidence RNAi screen, Co-IP, polysome profiling, ubiquitinase-dead mutant rescue

    PMID:25624349

    Open questions at the time
    • Structural basis of 4EHP recognition not determined
    • Ubiquitin chain type on 4EHP unspecified
  9. 2017 High

    Crystal structure of the HHARI–UbcH7~Ub complex revealed that a unique Zn²⁺-loop II steric wedge in RING1 forces the E2~Ub into an open conformation directing ubiquitin toward the E3 active site, mechanistically distinguishing RBR from canonical RING E3s.

    Evidence X-ray crystallography of HHARI/UbcH7~Ub, mutagenesis

    PMID:28552575

    Open questions at the time
    • No structure in CRL-activated state
    • Substrate engagement geometry unresolved
  10. 2018 High

    Genetic studies in Drosophila showed that Ari-1/ARIH1 mono-ubiquitinates the LINC complex component Koi to regulate myonuclear positioning, with functional rescue by human ARIH1 demonstrating conserved roles in nuclear organization.

    Evidence Drosophila loss-of-function genetics, in vitro/in vivo ubiquitination, cross-species rescue

    PMID:29689197

    Open questions at the time
    • Mammalian LINC complex substrate not validated
    • Mechanism by which mono-ubiquitination redistributes LINC complex unclear
  11. 2021 High

    ARIH1 was identified as the E3 ligase for PD-L1 degradation downstream of EGFR–GSK3α phosphorylation, establishing a direct role in immune checkpoint regulation and tumor immune evasion.

    Evidence Ubiquitination assays, phosphomimetic mutants, in vivo tumor models in immunocompetent vs. immunocompromised mice

    PMID:33879767

    Open questions at the time
    • Ubiquitin chain type on PD-L1 not fully resolved
    • CRL identity for PD-L1 ubiquitination not established
  12. 2022 High

    Three discoveries collectively expanded ARIH1's substrate repertoire and structural understanding: ISGylation of cGAS at K187 promoting oligomerization and antiviral immunity; ubiquitination of hnRNP-E1 driving EMT; and structural definition of the Rcat di-aromatic surface as the 4EHP-binding platform with phosphomimetic-driven auto-inhibition release.

    Evidence ARIH1 KO mice with viral infection (cGAS/ISG), yeast two-hybrid and Co-IP (hnRNP-E1), XL-MS/HDX-MS/NMR (4EHP binding)

    PMID:35102251 PMID:35716664 PMID:36217001

    Open questions at the time
    • ISGylation mechanism (how ARIH1 uses ISG15 instead of Ub) not biochemically dissected
    • hnRNP-E1 finding from single lab
    • Full-length activated ARIH1–CRL–substrate ternary structure unavailable
  13. 2023 High

    Two studies extended ARIH1's roles: ubiquitination and degradation of DNA-PKcs activates cGAS-STING and sensitizes tumors to PD-L1 blockade, while reconstitution showed ARIH1 catalyzes non-canonical serine ubiquitylation (oxyester bonds) with Rcat residues that differentially govern isopeptide vs. oxyester transfer.

    Evidence In vivo tumor models with ARIH1 KO/OE (DNA-PKcs); in vitro reconstitution with Rcat mutagenesis (Ser ubiquitylation)

    PMID:37429863 PMID:37870100

    Open questions at the time
    • Physiological Ser-ubiquitylation substrates not identified
    • Whether DNA-PKcs degradation is CRL-dependent not tested
  14. 2025 Medium

    Multiple studies in 2025–2026 demonstrated ARIH1 ubiquitinates HER2 (for lysosomal degradation), MFN2 (triggering mitophagy and ER stress), and PHB1 (K63-linked, promoting mitochondrial translocation), and that ARIH1 cooperates with Sec61β to recruit 4EHP for ER-associated translational quality control; reconstitution confirmed ARIH1 independently ubiquitinates PD-L1 and acts as a substrate receptor with CRLs.

    Evidence Co-IP and ubiquitination assays with KO models (HER2, MFN2, PHB1), liposome-based reconstitution (PD-L1), cap-binding assays and zebrafish rescue (Sec61β–4EHP)

    PMID:40285603 PMID:40472843 PMID:40960900 PMID:41123818 PMID:41593190

    Open questions at the time
    • Several findings from single labs awaiting independent replication
    • CRL identity for most new substrates unspecified
    • Structural basis for ARIH1 substrate receptor function not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of ARIH1 in its CRL-activated state bound to a physiological substrate is still lacking, and the rules governing substrate selection — including how the same E3 can ubiquitinate, ISGylate, or oxyester-modify distinct targets — remain undefined.
  • No cryo-EM/crystal structure of ternary ARIH1–neddylated CRL–substrate complex
  • Determinants that switch ARIH1 between ubiquitin and ISG15 conjugation unknown
  • Relative contribution of ARIH1 vs. CRL-associated RING in dual E3 complexes not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0016874 ligase activity 3
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 1
Partners
4EHPCGASDNA-PKCSHER2PD-L1SEC61ΒSQSTM1UBCH7
Complex memberships
Sec61β–ARIH1–4EHP translational repression complexneddylated CRL complexes

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 ARIH1 (HHARI) is a RING-between-RING (RBR) E3 ubiquitin ligase that functions as a RING/HECT hybrid: it binds the E2 enzyme UBCH7 via its RING1 domain, but transfers ubiquitin through an obligate thioester intermediate requiring a conserved cysteine in its RING2 domain, mechanistically distinct from canonical RING E3s. In vitro ubiquitination assays, active-site cysteine mutagenesis, biochemical characterization of E2~Ub thioester intermediates Nature High 21532592
1999 HHARI (ARIH1) interacts specifically with the E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8 via its N-terminal RING finger motif and IBR domain, but not with unrelated E2s (UbcH5, UbcH1), placing ARIH1 in the ubiquitin/proteasome pathway. Yeast two-hybrid screen, in vitro binding/pulldown assays The Journal of biological chemistry High 10521492
2001 HHARI (ARIH1) interacts and co-localizes with UbcH7 in mammalian cells, particularly in the perinuclear region; a minimal interaction region (residues 186–254) was defined, individual essential residues identified, and the distance between RING1 and IBR domains shown to be critical for binding. Mutation of RING1 from RING-HC to RING-H2 type abolishes UbcH7 interaction. Co-immunoprecipitation, co-localization by fluorescence microscopy, deletion and point mutagenesis The Journal of biological chemistry High 11278816
2013 HHARI (ARIH1), an Ariadne-subfamily RBR ligase, associates with neddylated Cullin-RING ligase (CRL) complexes; binding of the cognate neddylated CRL to HHARI greatly stimulates its RBR ligase activity in vitro (auto-ubiquitylation, E2~Ub thioester discharge, and ubiquitin-vinyl methyl ester reactivity), demonstrating that CRL neddylation is the activating signal for HHARI. In vitro ubiquitylation assays, activity-based probes (Ub-VME), biochemical co-association, genetic epistasis in vivo The EMBO journal High 24076655
2013 The crystal/solution structure of the HHARI RING2 (Rcat) domain was solved by NMR, revealing two Zn2+-binding sites and a single exposed catalytic cysteine. Structural comparison with HECT E3 NEDD4 shows a near-mirror image of catalytic residues, providing structural rationale for the RING/HECT hybrid mechanism; a conserved tandem aromatic pair near the C-terminus parallels the HECT ubiquitin-catalysis residue position. NMR structure determination, structural comparison PloS one Medium 24058416
2015 ARIH1 is upregulated after DNA damage via ATM-dependent attenuation of proteasomal degradation. Accumulated ARIH1 associates with 4EHP (a competitive inhibitor of eIF4E), promotes non-degradative ubiquitination of 4EHP, enriches in perinuclear ribosome-containing regions, and triggers 4EHP association with mRNA 5' caps, leading to translation arrest that protects cells from genotoxic stress. This mechanism requires ARIH1's ubiquitinase activity. RNAi screen, Co-IP, subcellular fractionation, polysome profiling, rescue with ubiquitinase-dead mutants, ATM inhibition Molecular and cellular biology High 25624349
2017 The HHARI RING1 domain contains a unique Zn2+-loop II extension absent in canonical RING E3s that acts as a steric wedge to enforce an open E2~Ub conformation, promoting Ub transfer to the E3 active-site cysteine rather than directly to substrate, mechanistically distinguishing RBR RING1 from canonical RING domains. X-ray crystallography of HHARI/UbcH7~Ub complex, structural comparison, mutagenesis Structure High 28552575
2018 Drosophila Ari-1 (ortholog of human ARIH1) mono-ubiquitinates the LINC complex member Koi, regulating LINC complex localization/distribution and myonuclear positioning; loss of Ari-1 causes nuclear clustering and morphology defects in larval muscles. Human ARIH1 rescues fly ari-1 mutant phenotypes, confirming functional conservation. Functional redundancy between Ari-1 and Parkin was demonstrated by cross-rescue. Genetic loss-of-function (Drosophila mutants), in vitro/in vivo ubiquitination assay, rescue experiments with human ARIH1, patient variant functional testing Developmental cell High 29689197
2021 ARIH1 acts as the E3 ubiquitin ligase responsible for ubiquitination and proteasomal degradation of PD-L1, downstream of EGFR-GSK3α signaling. GSK3α-mediated phosphorylation of PD-L1 at Ser279/Ser283 is required as a priming event before ARIH1-mediated ubiquitination. ARIH1 overexpression suppresses tumor growth and promotes cytotoxic T cell activation in immunocompetent but not immunocompromised mice. Ubiquitination assays, co-immunoprecipitation, phosphomimetic mutants, ARIH1 overexpression/knockdown in vivo and in vitro Nature communications High 33879767
2022 ARIH1 catalyzes mono-ISGylation of cGAS at Lys187, promoting cGAS oligomerization and activation, thereby enhancing type I interferon production during antiviral and autoimmune responses. Knockout of ARIH1 in mice causes hypersensitivity to HSV-1 infection and alleviates TREX1-deficiency-driven autoimmunity. ARIH1 KO/KD cell and mouse models, ISGylation assays, site-directed mutagenesis (K187), cGAS oligomerization assays, viral infection models Nature communications High 36217001
2022 ARIH1 interacts with hnRNP-E1 and promotes its ubiquitination and proteasomal degradation; ARIH1 silencing increases hnRNP-E1 protein stability and reduces hnRNP-E1 ubiquitination. ARIH1 promotes EMT induction, breast cancer cell invasion, and cancer stemness. Yeast two-hybrid, Co-IP, ubiquitination assays, ARIH1 KD/OE in breast cancer cell lines, in vivo tumor formation, miniTurboID proximity labeling Oncogene Medium 35102251
2022 The catalytic Rcat domain of HHARI (ARIH1) contains a di-aromatic surface that forms a direct binding platform for its substrate 4EHP, as established by XL-MS, HDX-MS, NMR, and biochemical assays. A phosphomimetic mutation on the Ariadne (auto-inhibitory) domain of HHARI promotes Rcat release and reorientation for transthiolation and substrate modification, providing a model for RBR substrate recognition. Cross-linking mass spectrometry (XL-MS), hydrogen-deuterium exchange MS (HDX-MS), NMR, biochemical ubiquitination assays, phosphomimetic mutagenesis Structure High 35716664
2023 ARIH1 mediates ubiquitination and proteasomal degradation of DNA-PKcs, triggering activation of the cGAS-STING pathway in tumors; this effect is blocked by a phospho-mimetic mutant (T68E/S213D) of cGAS. ARIH1-mediated STING activation promotes cytotoxic T cell infiltration and sensitizes tumors to PD-L1 blockade. Ubiquitination assays, co-immunoprecipitation, phosphomimetic mutants, ARIH1 KO/OE in vitro and in vivo tumor models, high-throughput drug screen Nature communications High 37429863
2023 ARIH1 catalyzes non-canonical serine ubiquitylation (oxyester bond formation) on CRL-bound substrates in addition to canonical lysine ubiquitylation. The efficiency of Ser ubiquitylation is dependent on the precise location and chemical environment of the serine within the substrate. Comprehensive mutagenesis of the ARIH1 Rcat domain identified residues critical for oxyester but not isopeptide bond formation. In vitro ubiquitylation reconstitution, mutagenesis of Rcat domain, biochemical analysis of ubiquitin-substrate linkage type The Biochemical journal High 37870100
2012 HHARI (ARIH1) is localized to both nucleus and cytoplasm, with higher nuclear levels; it co-localizes with nuclear bodies including Cajal bodies, PML bodies, and SC35 bodies. ARIH1 knockdown causes increased apoptosis, G2 arrest, and reductions in total cellular RNA, establishing a role in cellular proliferation. Antibody validation, immunofluorescence co-localization, siRNA knockdown with cell cycle and apoptosis readouts Experimental cell research Medium 23059369
2011 HHARI (ARIH1) binds several Parkin substrates in vitro (CDCrel-1, synphilin-1, CASK), forms aggresomes morphologically identical to Parkin-induced aggresomes (same subcellular localization, ubiquitin-proteasome components, microtubule dependence), and is found endogenously in human Lewy bodies in Parkinson's disease, suggesting redundant E3 ligase function with Parkin. In vitro binding assays, co-immunoprecipitation, immunofluorescence/aggresome formation assays, immunohistochemistry of human brain tissue Journal of molecular neuroscience Medium 21590270
2006 C. elegans ARI-1 (ortholog of human ARIH1) is an RBR ubiquitin ligase that interacts with UBC-18 (ortholog of UbcH7) via two-hybrid and functions with UBC-18 to regulate pharyngeal morphogenesis; genetic interactions identical to those of UBC-18 establish ARI-1 as the principal Ariadne-family E3 acting downstream of UBC-18 in pharyngeal development. Yeast two-hybrid, genetic analysis (double mutants), GFP reporter expression analysis Developmental biology Medium 16457801
2025 ARIH1 ubiquitinates PHB1 at lysine 186 via K63-linked ubiquitination through direct interaction with ARIH1's RING1+RBR+RING2 domains; this modification promotes PHB1 phosphorylation by Akt and subsequent mitochondrial translocation, maintaining mitochondrial stability and promoting oxidative phosphorylation in colorectal cancer cells. Co-immunoprecipitation, in vivo ubiquitination assays, domain mapping, site-directed mutagenesis, mitochondrial fractionation Advanced science Medium 40285603
2025 ARIH1 mediates ubiquitination and degradation of MFN2; in trophoblast cells, ARIH1 upregulation (as in preeclampsia/hypoxia) leads to MFN2 degradation, triggering mitophagy and endoplasmic reticulum stress that impair trophoblast proliferation and invasion. ARIH1 KD/OE in trophoblast cell lines, ubiquitination assays, PE rat model, mitochondrial membrane potential assay, ERS markers FASEB journal Medium 40960900
2023 ARIH1 enhances antiviral immunity against influenza A virus by stabilizing RIG-I through interaction with SQSTM1/p62, preventing RIG-I degradation and promoting IFN-β and downstream ISG expression. Co-immunoprecipitation, ubiquitination assays, TCID50, luciferase reporter assays, ARIH1 KD experiments Virology journal Medium 37005687
2025 ARIH1 deficiency in mice causes impaired spatial learning and memory due to upregulation of GIRK2 in dorsal hippocampal CaMKII-expressing neurons, attributed to impaired ARIH1-mediated ubiquitination and degradation of GIRK2. Selective ARIH1 knockdown in CaMKII+ (but not PV+ or SST+) hippocampal neurons recapitulates the memory deficit; GIRK channel inhibition rescues the phenotype. ARIH1 KO mouse, lentiviral ARIH1 restoration, neuron-type-specific knockdown, GIRK inhibitor rescue, Morris water maze/novel object recognition bioRxivpreprint Medium bio_10.1101_2025.03.10.625121
2025 ARIH1 directly targets RIG-I in a neddylation-dependent manner to stimulate IFN-β secretion. The unique acidic N-terminal/UBA-like domain of HHARI is required for RIG-I activation and interferon signaling; truncated HHARI containing only these domains retains IFN-stimulating activity. Overexpression of cullins 1–5 enhances ARIH1-mediated IFN-β secretion, suggesting the N-terminus activates neddylated CRL complexes which in turn activate HHARI itself. HHARI deletion mutants, neddylation inhibitors, cullin overexpression, IFN-β reporter assays, co-immunoprecipitation bioRxivpreprint Low bio_10.1101_2025.02.01.636034
2026 ARIH1 is recruited by Sec61β (a translocon component) along with 4EHP to repress translation of ER-targeted (ERpQC substrate) mRNAs by blocking eIF4E binding to the mRNA 5' cap; the Sec61β-ARIH1-4EHP complex is required for cytoplasmic proteostasis under ER stress. Co-immunoprecipitation, mRNA cap-binding assays, ARIH1 KD/rescue, zebrafish motor function assay with ARIH1 overexpression EMBO reports Medium 41593190
2025 ARIH1 promotes HER2 ubiquitination through direct interaction between ARIH1 and HER2 (enhanced by pyrotinib treatment), leading to lysosomal degradation of HER2 in HER2-positive NSCLC cells; ARIH1 KO abolishes pyrotinib-induced HER2 degradation and tumor suppression in vivo. Co-immunoprecipitation, ubiquitination assays, LC-MS/MS, ARIH1 KO in xenograft models Cellular oncology Medium 41123818
2025 In vitro reconstitution with purified components shows that ARIH1, rather than CRL3SPOP, independently ubiquitinates the cytoplasmic domain of PD-L1. ARIH1 also acts as a substrate receptor cooperating with CRLs to catalyze PD-L1 ubiquitination; phosphorylation of PD-L1 enhances its ubiquitination by disrupting membrane association, as shown using liposome-based enzymatic assays. In vitro ubiquitylation reconstitution with purified components, liposome assays, biochemical comparison of E3 ligase activities Structure High 40472843

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 454 21532592
1993 ARI 1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii. International journal of antimicrobial agents 175 18611526
2000 Sequence analysis of ARI-1, a novel OXA beta-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92. Antimicrobial agents and chemotherapy 172 10602749
2020 CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies. Molecular therapy : the journal of the American Society of Gene Therapy 131 33010231
2020 Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial. Frontiers in immunology 111 32528460
2021 ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation. Nature communications 102 33879767
1999 The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1. The Journal of biological chemistry 101 10521492
2013 TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. The EMBO journal 97 24076655
2014 An evaluation of genotyping by sequencing (GBS) to map the Breviaristatum-e (ari-e) locus in cultivated barley. BMC genomics 84 24498911
2001 Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7. The Journal of biological chemistry 69 11278816
2015 Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference. PLoS genetics 65 26291793
2022 The E3 ubiquitin ligase ARIH1 promotes antiviral immunity and autoimmunity by inducing mono-ISGylation and oligomerization of cGAS. Nature communications 58 36217001
2023 ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade. Nature communications 46 37429863
2022 The hospital exemption pathway for the approval of advanced therapy medicinal products: an underused opportunity? The case of the CAR-T ARI-0001. Bone marrow transplantation 46 35046545
2017 Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1. Structure (London, England : 1993) 46 28552575
1996 Nerve fiber regeneration following axotomy in the diabetic biobreeding Worcester rat: the effect of ARI treatment. Journal of diabetes and its complications 42 8835917
2018 Ari-1 Regulates Myonuclear Organization Together with Parkin and Is Associated with Aortic Aneurysms. Developmental cell 41 29689197
2019 Novel ROR1 inhibitor ARI-1 suppresses the development of non-small cell lung cancer. Cancer letters 38 31125641
1999 Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RI alpha subunit: p53-independent mechanism of action. Molecular and cellular biochemistry 36 10395066
2015 The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. Molecular and cellular biology 35 25624349
2021 Is Hospital Exemption an Alternative or a Bridge to European Medicines Agency for Developing Academic Chimeric Antigen Receptor T-Cell in Europe? Our Experience with ARI-0001. Human gene therapy 34 34476985
2020 Ventilation and laboratory confirmed acute respiratory infection (ARI) rates in college residence halls in College Park, Maryland. Environment international 31 32028176
2022 The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression. Oncogene 29 35102251
1990 Diabetic autonomic neuropathy in BB rats and effect of ARI treatment on heart-rate variability and vagus nerve structure. Diabetes 29 2110085
2006 ARI-1, an RBR family ubiquitin-ligase, functions with UBC-18 to regulate pharyngeal development in C. elegans. Developmental biology 27 16457801
2009 Identification and genomic location of a reniform nematode (Rotylenchulus reniformis) resistance locus (Ren ari) introgressed from Gossypium aridum into upland cotton (G. hirsutum). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 24 19830404
2022 Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter's Transformation. Frontiers in oncology 23 35174095
2022 Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. Frontiers in immunology 22 36275777
2012 Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies. Experimental cell research 22 23059369
2009 A mechanistic basis for the coordinated regulation of pharyngeal morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18-ARI-1. PLoS genetics 22 19521497
2022 Results of ARI-0001 CART19 cell therapy in patients with relapsed/refractory CD19-positive acute lymphoblastic leukemia with isolated extramedullary disease. American journal of hematology 19 35253928
2019 5-ARI induces autophagy of prostate epithelial cells through suppressing IGF-1 expression in prostate fibroblasts. Cell proliferation 19 30883989
2021 Reply to the commentary by Ben-Ari and Delpire: Bumetanide and neonatal seizures: Fiction versus reality. Epilepsia 18 33764535
2016 Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution. Journal of ultrasound 18 27635163
2016 Marker development using SLAF-seq and whole-genome shotgun strategy to fine-map the semi-dwarf gene ari-e in barley. BMC genomics 15 27835941
2011 The parkin-like human homolog of Drosophila ariadne-1 (HHARI) can induce aggresome formation in mammalian cells and is immunologically detectable in Lewy bodies. Journal of molecular neuroscience : MN 15 21590270
1994 Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy. Diabetes research and clinical practice 15 7821191
2017 Evolution in situ of ARI-A in pB2-1, a type 1 IncC plasmid recovered from Klebsiella pneumoniae, and stability of Tn4352B. Plasmid 14 29050976
2013 Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase. PloS one 14 24058416
2023 The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma. British journal of haematology 13 37905734
2017 Removal of estrone, 17β-estradiol, and estriol from sewage and cow dung by immobilized Novosphingobium sp. ARI-1. Environmental technology 13 28707514
2022 Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain. Structure (London, England : 1993) 12 35716664
2016 pDGO100, a type 1 IncC plasmid from 1981 carrying ARI-A and a Tn1696-like transposon in a novel integrating element. Plasmid 11 27318267
2023 Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase. The Biochemical journal 8 37870100
2023 ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62. Virology journal 5 37005687
2025 The E3 Ubiquitin Ligase ARIH1 Facilitates Colorectal Cancer Progression by Promoting Oxidative Phosphorylation via the Mitochondrial Translocation of K63-Linked Ubiquitinated PHB1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40285603
2024 Epidemic profile of common respiratory viruses in association SARS CoV-2 among SARI and ARI-two year study. Molecular biology reports 4 38252354
2020 Genetic dissection of the interactions between semi-dwarfing genes sdw1 and ari-e and their effects on agronomic traits in a barley MAGIC population. Molecular breeding : new strategies in plant improvement 4 40255936
2025 ARIH1 Inhibition Promotes Microtubule Stability and Sensitizes Breast Cancer Cells to Microtubule-Stabilizing Agents. Cancers 3 40075632
2025 Molecular epidemiological characterization of human bocavirus (HBoV) in acute respiratory infection (ARI) patients in Yucheng, China. Frontiers in public health 3 40260169
2025 International consensuses and guidelines on central serous chorioretinopathy (CSC) by the Asia Pacific Vitreo-retina Society (APVRS), the Academy of Asia-Pacific Professors of Ophthalmology (AAPPO) and the Academia Retina Internationalis (ARI). Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) 3 41106484
2023 CADD Studies in the Discovery of Potential ARI (Aldose Reductase Inhibitors) Agents for the Treatment of Diabetic Complications. Current diabetes reviews 3 35993470
1988 Lectins and their role in a new polyvalent bacterial vaccine against ARI. Zentralblatt fur Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical microbiology, infectious diseases, virology, parasitology 3 3223136
2025 Biochemical analysis of PD-L1 ubiquitination by CRL3SPOP, ARIH1, and NEDD4 family ubiquitin ligases. Structure (London, England : 1993) 2 40472843
2017 Salmonella ubiquitination: ARIH1 enters the fray. EMBO reports 2 28821533
1991 Peripheral nerve repair following ARI treatment. Advances in experimental medicine and biology 2 1656713
2025 T-cell responses against CD19-targeted CAR T cells varnimcabtagene autoleucel (ARI-0001): implications for immune response and therapy outcomes. Journal for immunotherapy of cancer 1 40987492
2016 A novel laser-induced fluorescence scheme for Ar-I in a plasma. The Review of scientific instruments 1 26827319
2026 Sec61β maintains cytoplasmic proteostasis via ARIH1-mediated translational repression upon ER stress. EMBO reports 0 41593190
2025 Analysis of Gene Polymorphisms in Benign Prostate Hyperplasia Patients Receiving Combination Therapy of Alpha Blocker (a-Blocker) and 5-Alpha Reductase Inhibitor (5-ARI). Acta informatica medica : AIM : journal of the Society for Medical Informatics of Bosnia & Herzegovina : casopis Drustva za medicinsku informatiku BiH 0 40223852
2025 ARIH1 Promotes Preeclampsia by Inducing MFN2-Dependent Hypoxia-Triggered Mitophagy and Endoplasmic Reticulum Stress in Trophoblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40960900
2025 Pyrotinib inhibits the tumorigenicity of HER2-positive non-small cell lung cancer by inducing ARIH1/ubiquitin/lysosome-dependent degradation of HER2. Cellular oncology (Dordrecht, Netherlands) 0 41123818
2024 Determination of the Allelic Composition of the sdw1/denso (HvGA20ox2), uzu1 (HvBRI1) and ari-e (HvDep1) Genes in Spring Barley Accessions from the VIR Collection. Plants (Basel, Switzerland) 0 38337909
2016 Hari Shroff: Taking a closer look. The Journal of cell biology 0 27528653
2014 [Optimization of hydrolysis process of linarin using response surface methodology and research about ARI activity of glycosylation-acacetin]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 0 25272843
2013 HHARI is one HECT of a RING. Structure (London, England : 1993) 0 23747110