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Showing ARIH1 — HHARI is a alias.

ARIH1

E3 ubiquitin-protein ligase ARIH1 · UniProt Q9Y4X5

Length
557 aa
Mass
64.1 kDa
Annotated
2026-06-09
69 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARIH1 (HHARI) is a RING-between-RING (RBR) E3 ubiquitin ligase that operates by a RING/HECT hybrid mechanism: it binds its cognate E2 (UbcH7/UbcH8) through its RING1 domain but transfers ubiquitin via an obligate thioester intermediate at a conserved catalytic cysteine in the RING2 (Rcat) domain, mechanistically distinguishing RBR ligases from canonical RING E3s (PMID:21532592, PMID:10521492). Structural work explains each step of this cycle—the RING2 fold positions a single exposed catalytic cysteine in a near-mirror image of HECT active sites (PMID:24058416), a unique Zn2+-loop II extension in RING1 acts as a steric wedge that enforces an open E2~Ub conformation favoring transthiolation (PMID:28552575), and the Rcat domain presents a di-aromatic substrate-binding platform whose engagement is gated by release of the autoinhibitory Ariadne domain (PMID:35716664). ARIH1 is activated by neddylated Cullin-RING ligase (CRL) complexes, which stimulate its ligase activity and couple it to CRL-bound substrates (PMID:24076655), and it can catalyze non-canonical serine (oxyester) ubiquitylation in addition to canonical lysine isopeptide linkages (PMID:37870100). Through this chemistry ARIH1 modifies a broad substrate repertoire to control distinct cellular outcomes: it ubiquitinates 4EHP to drive translational arrest under genotoxic stress and, with Sec61β, assembles a 5' cap complex that selectively represses ER-targeted mRNA translation during ER stress (PMID:25624349, PMID:41593190); it promotes proteasomal degradation of phosphorylated PD-L1 and of DNA-PKcs to enhance antitumor immunity (PMID:33879767, PMID:37429863); it mono-ISGylates cGAS at K187 to potentiate innate immune signaling (PMID:36217001); and it mono-ubiquitinates the LINC-complex protein Koi to regulate nuclear positioning, a function shared and rescued across species (PMID:29689197). Patient-derived ARIH1 variants fail to rescue this conserved activity, linking the protein to developmental phenotypes (PMID:29689197).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 Medium

    Establishing which E2 enzymes ARIH1 partners with defined the first step of its catalytic cycle and the specificity of RBR ligases.

    Evidence Yeast two-hybrid screen and in vitro binding assays mapping RING1/IBR interaction with UbcH7 and UbcH8

    PMID:10521492

    Open questions at the time
    • Did not establish the catalytic mechanism of ubiquitin transfer
    • No substrate identified
  2. 2001 Medium

    Defining the minimal RING1-UbcH7 interaction surface and its requirement for a RING-HC architecture connected E2 selectivity to a structural determinant.

    Evidence Reciprocal co-IP, immunofluorescence co-localization, and point mutagenesis in mammalian cells

    PMID:11278816

    Open questions at the time
    • Functional consequence of perinuclear localization not addressed
    • Did not link binding to catalytic output
  3. 2011 High

    Resolving how ARIH1 transfers ubiquitin reclassified it as a RING/HECT hybrid, answering whether RBR ligases use direct E2-to-substrate transfer or an enzyme thioester intermediate.

    Evidence In vitro ubiquitin transfer assays with active-site cysteine mutagenesis across RBR family members

    PMID:21532592

    Open questions at the time
    • Did not explain how the open E2~Ub conformation is enforced
    • Physiological substrates and activation unknown
  4. 2013 High

    Discovery that neddylated CRLs bind and stimulate ARIH1 placed the enzyme into the cullin pathway and explained how a basally autoinhibited ligase is activated.

    Evidence Co-IP, in vitro auto-ubiquitylation, thioester discharge, activity-based probe reactivity, and in vivo CRL activity assays

    PMID:24076655

    Open questions at the time
    • Structural basis of CRL-mediated activation not resolved
    • Substrate range conferred by CRLs not defined
  5. 2013 High

    The RING2 NMR structure provided the structural rationale for the HECT-like catalytic cysteine arrangement.

    Evidence NMR solution structure of the HHARI RING2 domain with comparison to HECT ligase NEDD4

    PMID:24058416

    Open questions at the time
    • Did not capture the active conformation in context of full-length ligase
    • Substrate-binding surface not defined
  6. 2015 Medium

    Identifying 4EHP ubiquitination as a non-degradative output linked ARIH1 to translational control during genotoxic stress, extending its role beyond proteasomal targeting.

    Evidence RNAi with WT vs. catalytic-mutant rescue, ARIH1-4EHP co-IP, subcellular fractionation, and mRNA translation/viability assays

    PMID:25624349

    Open questions at the time
    • Ubiquitination site on 4EHP and chain type not defined
    • Mechanism of ATM-mediated ARIH1 stabilization not detailed
  7. 2017 High

    Capturing the HHARI/UbcH7~Ub complex explained how RING1 promotes transthiolation rather than direct substrate ubiquitination.

    Evidence X-ray crystallography of the HHARI/UbcH7~Ub complex with mutagenesis and biochemical validation

    PMID:28552575

    Open questions at the time
    • Did not address substrate recruitment to RING2
    • Activation by CRLs not structurally integrated
  8. 2018 High

    Demonstrating that the conserved ortholog mono-ubiquitinates the LINC protein Koi defined a developmental, nuclear-positioning function and connected ARIH1 variants to phenotype via cross-species rescue.

    Evidence Drosophila loss-of-function and rescue genetics, ubiquitination assays, and immunofluorescence of LINC members

    PMID:29689197

    Open questions at the time
    • Specific human disease entity not delineated in this work
    • Whether Koi-equivalent regulation occurs in mammalian cells not shown
  9. 2021 Medium

    Identifying ARIH1 as the E3 for phosphorylated PD-L1 connected it to immune checkpoint regulation and antitumor immunity.

    Evidence Co-IP, ubiquitination assays, ARIH1 OE/KD in tumor models, syngeneic in vivo experiments, and drug screen

    PMID:33879767

    Open questions at the time
    • Dependence on CRL scaffolding not resolved here
    • Direct vs. indirect catalysis not biochemically isolated
  10. 2022 High

    Discovery that ARIH1 mono-ISGylates cGAS at K187 established a non-ubiquitin modification activity driving innate immune activation.

    Evidence ISGylation assays, K187 mutagenesis, conditional Arih1 KO mice, and HSV-1/TREX1-deficient models

    PMID:36217001

    Open questions at the time
    • Structural basis for ISG15 vs. ubiquitin transfer not defined
    • How substrate choice between modifications is determined unknown
  11. 2022 High

    Defining the di-aromatic Rcat substrate platform and Ariadne-release gating produced a general model for how RBR ligases recruit and modify substrates.

    Evidence XL-MS, HDX-MS, NMR, and biochemical binding/ubiquitination assays with phosphomimetic mutagenesis

    PMID:35716664

    Open questions at the time
    • The physiological kinase relieving Ariadne autoinhibition not identified
    • Generality across all substrates not tested
  12. 2022 Medium

    Showing ARIH1-mediated degradation of hnRNP-E1 linked the ligase to EMT and cancer stemness.

    Evidence Yeast two-hybrid, KD/OE in mammary cells, ubiquitination assays, miniTurboID, and in vivo tumor assays

    PMID:35102251

    Open questions at the time
    • Ubiquitination site and chain type on hnRNP-E1 not defined
    • CRL dependence not established
  13. 2023 Medium

    Identifying DNA-PKcs as an ARIH1 degradation substrate connected the ligase to STING-pathway activation and T cell infiltration.

    Evidence Co-IP, ubiquitination assays, ARIH1 OE/KD, syngeneic tumor models, and drug screen

    PMID:37429863

    Open questions at the time
    • Direct catalysis vs. CRL recruitment not separated
    • Ubiquitination site on DNA-PKcs not mapped
  14. 2023 High

    Demonstrating serine (oxyester) ubiquitylation expanded the chemical repertoire of ARIH1 beyond lysine isopeptide bonds and identified active-site residues controlling linkage chemistry.

    Evidence In vitro reconstitution with purified components and comprehensive Rcat-domain mutagenesis comparing Ser vs. Lys ubiquitylation

    PMID:37870100

    Open questions at the time
    • Physiological substrates of Ser ubiquitylation not identified
    • Cellular relevance of oxyester linkages not established
  15. 2025 High

    Reconstitution showed ARIH1 can ubiquitinate PD-L1 both independently and cooperatively with CRLs, and that substrate phosphorylation/membrane disengagement controls modification.

    Evidence In vitro reconstitution with purified ARIH1/CRL3SPOP/NEDD4 and liposome-based phosphomimetic assays

    PMID:40472843

    Open questions at the time
    • Relative contribution of CRL-dependent vs. independent activity in cells unknown
    • Cellular determinants of PD-L1 phosphorylation not addressed
  16. 2025 Medium

    Identifying K63-linked ubiquitination of PHB1 connected ARIH1 to mitochondrial function via a non-degradative signal in colorectal cancer.

    Evidence Co-IP, in vitro ubiquitination, K186 mutagenesis, subcellular fractionation, and mitochondrial function assays

    PMID:40285603

    Open questions at the time
    • How K63 linkage drives Akt phosphorylation of PHB1 mechanistically unclear
    • CRL involvement not tested
  17. 2025 Medium

    Mouse genetics tied ARIH1-mediated degradation of GIRK2 to learning and memory in hippocampal CaMKII neurons.

    Evidence Heterozygous KO, cell-type-specific KD, lentiviral rescue, ubiquitination assays, and behavioral testing (preprint)

    PMID:bio_10.1101_2025.03.10.625121

    Open questions at the time
    • Not yet peer-reviewed
    • Ubiquitination site on GIRK2 not mapped
    • Direct catalysis vs. indirect regulation not isolated
  18. 2026 Medium

    Defining the Sec61β-ARIH1-4EHP cap complex revealed how ARIH1 imposes selective translational repression of ER-targeted mRNAs during ER stress.

    Evidence Co-IP of the ternary complex, cap-binding assays, Sec61β KD, and ARIH1-rescued zebrafish motor phenotypes

    PMID:41593190

    Open questions at the time
    • Whether ARIH1 catalytic activity is required for repression not isolated here
    • Substrate of ubiquitination within the complex not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARIH1 selects among its many substrates and chooses between ubiquitin, ISG15, lysine vs. serine modification, and degradative vs. non-degradative chain types in a given cellular context remains unresolved.
  • No unified model linking CRL identity to substrate choice
  • Physiological signals gating Ariadne autoinhibition release not mapped
  • Determinants of modification chemistry (Ub vs. ISG15, Lys vs. Ser) in cells unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0031386 protein tag activity 1
Localization
GO:0005634 nucleus 1 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 2
Partners
4EHPCUL1MFN2NCOA4PHB1SEC61BSQSTM1UBE2L3
Complex memberships
Sec61β–ARIH1–4EHP cap complexneddylated Cullin-RING ligase (CRL) complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 HHARI (ARIH1) functions as a RING/HECT hybrid E3 ligase: it binds E2 (UBCH7) via its RING1 domain but transfers ubiquitin through an obligate thioester intermediate at a conserved cysteine in the RING2 domain, classifying RBR ligases as mechanistically distinct from canonical RING E3s. In vitro ubiquitin transfer assays, active-site cysteine mutagenesis, biochemical characterization of E2-E3 pairs Nature High 21532592
1999 HHARI (ARIH1) interacts specifically with UbcH7 and UbcH8 (but not UbcH5 or UbcH1) via its N-terminal RING1 finger motif and IBR domain, identified by yeast two-hybrid screen and confirmed by in vitro binding studies. Yeast two-hybrid screen, in vitro binding assays (pulldown) The Journal of biological chemistry Medium 10521492
2001 HHARI (ARIH1) co-localizes with UbcH7 in the perinuclear region of mammalian cells; a minimal interaction region (residues 186–254) was defined, specific amino acid residues essential for the RING1–UbcH7 interaction were identified, and conversion of RING1 from RING-HC to RING-H2 type abolishes interaction. Co-immunoprecipitation in mammalian cells, co-localization by immunofluorescence, deletion/point mutagenesis The Journal of biological chemistry Medium 11278816
2013 HHARI (ARIH1) and TRIAD1, Ariadne-subfamily RBR ligases, associate with distinct neddylated Cullin-RING ligase (CRL) complexes; neddylated CRL binding greatly stimulates HHARI RBR ligase activity in vitro (auto-ubiquitylation, thioester discharge, ubiquitin-vinyl methyl ester reactivity), and RBR ligase activity reciprocally impacts CRL levels and activities in vivo. Co-immunoprecipitation, in vitro ubiquitylation assays, ubiquitin-vinyl methyl ester reactivity, genetic (in vivo) CRL activity assays The EMBO journal High 24076655
2013 The NMR solution structure of the HHARI RING2 domain was determined, revealing two Zn2+-binding sites, a single exposed catalytic cysteine, and a near-mirror-image arrangement of catalytic residues compared to HECT E3 ligase NEDD4, providing structural rationale for the RING/HECT hybrid mechanism. NMR structure determination, structural comparison with HECT E3 ligases PloS one High 24058416
2015 ARIH1 protects cells against genotoxic stress by promoting non-degradative ubiquitination of 4EHP (a competitive eIF4E inhibitor), localizing to perinuclear ribosome-containing regions after DNA damage, and inducing mRNA translation arrest in an ARIH1 ubiquitin-ligase-activity-dependent manner; ATM signaling stabilizes ARIH1 protein by attenuating its proteasomal degradation. RNAi screen, expression of wild-type vs. ubiquitinase-defective ARIH1 mutants, subcellular fractionation, co-immunoprecipitation (ARIH1–4EHP), mRNA translation assays, cell viability assays Molecular and cellular biology Medium 25624349
2017 Crystal/structural studies showed that HHARI RING1 contains a unique Zn2+-loop II extension (not present in canonical RING E3s) that acts as a steric wedge to enforce an open E2~Ub conformation, explaining how RBR RING1 promotes Ub transfer to the E3 active-site cysteine rather than directly to substrate. X-ray crystallography of HHARI/UbcH7~Ub complex, mutagenesis, biochemical validation Structure High 28552575
2018 Drosophila Ari-1 (ortholog of ARIH1) mono-ubiquitinates the LINC complex member Koi, regulating myonuclear positioning; Ari-1 and Parkin are functionally redundant for this process (each rescues the other's mutant phenotype); human ARIH1 rescues fly ari-1 mutants whereas patient-derived ARIH1 variants fail to do so. Drosophila genetics (loss-of-function, rescue experiments), in vitro/in vivo ubiquitination assays (mono-ubiquitination of Koi), immunofluorescence of LINC complex members Developmental cell High 29689197
2021 ARIH1 is the E3 ubiquitin ligase that ubiquitinates PD-L1 following GSK3α-mediated phosphorylation at Ser279/Ser283, targeting PD-L1 for proteasomal degradation; ARIH1 overexpression suppresses tumor growth and promotes cytotoxic T cell activation in immunocompetent but not immunocompromised mice. Co-immunoprecipitation, ubiquitination assays, ARIH1 overexpression/knockdown in tumor models, in vivo syngeneic tumor experiments, high-throughput drug screen Nature communications Medium 33879767
2022 ARIH1 catalyzes mono-ISGylation of cGAS at K187, which promotes cGAS oligomerization and activation, thereby enhancing type I interferon and proinflammatory cytokine production in response to HSV-1 or cytoplasmic DNA; conditional Arih1 knockout mice are hypersensitive to HSV-1 and show reduced autoimmune phenotypes in TREX1-deficient background. Co-immunoprecipitation, ISGylation assays, ARIH1 KO/KD (siRNA, conditional mouse knockouts), HSV-1 infection models, site-directed mutagenesis (K187) Nature communications High 36217001
2022 ARIH1 ubiquitinates hnRNP-E1, promoting its degradation and thereby facilitating EMT induction; ARIH1 silencing increases hnRNP-E1 stability and reduces ubiquitination, delays EMT and invasion, while ARIH1 overexpression promotes EMT and invasion; ARIH1 silencing in breast cancer cells reduces cancer stem cell properties in vitro and tumor formation in vivo. Yeast two-hybrid (interaction identification), ARIH1 KD/OE in mammary epithelial and breast cancer cell lines, ubiquitination assays, miniTurboID proximity labeling, in vivo tumor formation assays Oncogene Medium 35102251
2022 The HHARI (ARIH1) Rcat (RING2) domain contains a di-aromatic surface that forms a binding platform for substrate recruitment (demonstrated for 4EHP); a phosphomimetic mutation on the auto-inhibitory Ariadne domain promotes Rcat release and reorientation enabling transthiolation and substrate modification, defining a general model for RBR substrate recognition. XL-MS, HDX-MS, NMR, biochemical binding and ubiquitination assays, phosphomimetic mutagenesis Structure High 35716664
2023 ARIH1 mediates ubiquitination and proteasomal degradation of DNA-PKcs, thereby activating the STING pathway and promoting cytotoxic T cell infiltration; a phospho-mimetic mutant of cGAS (T68E/S213D) blocks this ARIH1-DNA-PKcs-STING signaling axis. Co-immunoprecipitation, ubiquitination assays, ARIH1 overexpression/knockdown, syngeneic in vivo tumor models, high-throughput drug screen Nature communications Medium 37429863
2023 ARIH1 catalyzes serine (oxyester) ubiquitylation in addition to canonical lysine (isopeptide) ubiquitylation on CRL-bound substrates; efficiency of Ser ubiquitylation is highly dependent on local sequence context; comprehensive mutagenesis of the Rcat domain identified residues differentially affecting oxyester vs. isopeptide bond formation. In vitro reconstitution with purified components, comprehensive active-site mutagenesis of Rcat domain, biochemical ubiquitylation assays measuring Ser vs. Lys ubiquitylation The Biochemical journal High 37870100
2023 ARIH1 interacts with SQSTM1/p62 and enhances RIG-I stability (via p62-mediated pathway), thereby promoting IFN-β and downstream ISG expression during influenza A virus infection; ARIH1 is upregulated during IAV infection. Co-immunoprecipitation, Western blot, TCID50 viral titer assay, luciferase reporter assay, siRNA knockdown Virology journal Low 37005687
2006 C. elegans ARI-1 (ARIH1 ortholog) functions as an RBR ubiquitin ligase with UBC-18 (ortholog of UbcH7) to control pharyngeal morphogenesis; genetic interactions show ARI-1 is the principal Ariadne family member for this process, and GFP reporters show dynamic expression in muscles and neurons. Yeast two-hybrid (ARI-1/UBC-18 interaction), C. elegans genetic analysis (double mutants, RNAi), GFP reporter expression Developmental biology Medium 16457801
2009 In C. elegans, UBC-18 (UbcH7 ortholog)–ARI-1 (ARIH1 ortholog) complex acts in ubiquitin-mediated proteolysis to negatively regulate SUP-35 abundance, functioning redundantly with LIN-35/Rb (which acts as a transcriptional repressor of sup-35) to control pharyngeal morphogenesis; genetic suppressor analysis showed sup-35 mutations revert synthetic lethality of ubc-18; pha-1 double mutants. Genetic epistasis analysis, double/triple mutant analysis, molecular analysis of SUP-35 abundance PLoS genetics Medium 19521497
2012 HHARI (ARIH1) localizes to both nucleus and cytoplasm, with higher nuclear levels; it co-localizes with Cajal bodies (p80 coilin, NOPP140), PML bodies, and SC35 bodies; ARIH1 knockdown causes reduced proliferation, increased apoptosis, G2 cell cycle arrest, and reduced total cellular RNA levels. Antibody-based immunofluorescence, RNAi knockdown screen, flow cytometry (cell cycle analysis), RNA quantification Experimental cell research Medium 23059369
2011 HHARI (ARIH1) binds many of the same substrate proteins as parkin (including CDCrel-1, synphilin-1, and CASK) in vitro, forms aggresomes morphologically indistinguishable from parkin-induced aggresomes (microtubule-dependent, containing ubiquitin-proteasome components), and is detected in human Lewy bodies in Parkinson's disease tissue. In vitro binding assays (pulldown), cell-based aggresome formation assays, immunofluorescence, immunohistochemistry of human brain tissue Journal of molecular neuroscience Low 21590270
2025 ARIH1 directly interacts with PHB1 via its RING1+RBR+RING2 domains and catalyzes K63-linked ubiquitination of PHB1 at K186; this modification promotes PHB1 phosphorylation by Akt and mitochondrial translocation of PHB1, maintaining mitochondrial stability and promoting oxidative phosphorylation in colorectal cancer cells. Co-immunoprecipitation, in vitro ubiquitination assays, site-directed mutagenesis (K186), subcellular fractionation, mitochondrial function assays Advanced science Medium 40285603
2025 ARIH1 independently ubiquitinates PD-L1 in vitro (without requiring CRL as scaffold) and also cooperates with CRLs to catalyze PD-L1 ubiquitination; phosphorylation of PD-L1 enhances ubiquitination by disrupting its membrane association (demonstrated using liposomes); NEDD4 family E3s also ubiquitinate PD-L1. In vitro reconstitution with purified components (ARIH1, CRL3SPOP, NEDD4), liposome-based enzymatic assays, phosphorylation-mimetic mutants Structure High 40472843
2025 ARIH1 mediates ubiquitination and degradation of MFN2, promoting mitophagy and endoplasmic reticulum stress in trophoblasts under hypoxia/reoxygenation conditions; ARIH1 inhibition reverses suppressed proliferation/invasion and reduces ROS, and MFN2 inhibition abolishes the protective effects of ARIH1 downregulation. Co-immunoprecipitation, ubiquitination assays, ARIH1 KD/overexpression, in vivo PE rat model, HTR8 cell hypoxia/reoxygenation model FASEB journal Low 40960900
2025 ARIH1 interacts with NCOA4 and promotes its K48-linked ubiquitination and proteasomal degradation, thereby suppressing ferritinophagy and ferroptosis in lung adenocarcinoma; ARIH1 loss results in iron accumulation, lipid peroxidation, glutathione depletion, and ferroptotic cell death. Co-immunoprecipitation, ubiquitination assays (K48-linkage), cycloheximide chase, siRNA knockdown, ferroptosis marker assays Respiratory research Low 42169065
2025 ARIH1 regulates learning and memory in mice by ubiquitinating and promoting degradation of GIRK2 in dorsal hippocampal CaMKII-expressing neurons; ARIH1 deficiency causes GIRK2 upregulation and spatial learning/memory deficits that are rescued by lentiviral ARIH1 restoration or GIRK channel inhibition; selective ARIH1 KD in CaMKII+ (but not PV+ or SST+) neurons recapitulates the memory deficit. ARIH1 heterozygous knockout mouse model, lentiviral ARIH1 rescue, cell-type-specific ARIH1 knockdown (CaMKII/PV/SST-Cre), ubiquitination assays, Morris water maze, novel object recognition, GIRK channel pharmacology bioRxivpreprint Medium bio_10.1101_2025.03.10.625121
2025 HHARI (ARIH1) stimulates IFN-β secretion by directly targeting RIG-I in a neddylation-dependent manner; the acidic N-terminal/UBA-like domains of HHARI are essential for this pro-interferon activity and for interaction with neddylated cullins; truncated HHARI containing only the N-terminal domains retains neddylation-dependent interferon signaling; overexpression of cullins 1–5 enhances HHARI-mediated IFN-β secretion. HHARI truncation mutants, neddylation inhibitor experiments, overexpression of cullins, IFN-β secretion assays, RIG-I interaction studies bioRxivpreprint Low bio_10.1101_2025.02.01.636034
2025 ARIH1 loss leads to MAP4 upregulation and microtubule stabilization (increased tubulin acetylation and enhanced spindle organization) in breast cancer cells, sensitizing them to paclitaxel; this identifies ARIH1 as a regulator of microtubule dynamics. ARIH1 siRNA knockdown in breast cancer cell lines, tubulin acetylation assays, MAP4 protein level measurement, paclitaxel sensitivity assays (viability, colony formation, apoptosis) Cancers Low 40075632
2025 Pyrotinib enhances interaction between ARIH1 and HER2, promoting HER2 ubiquitination and endocytosis leading to lysosomal degradation of HER2 in HER2-positive NSCLC; tumor growth suppression by pyrotinib in vivo is ARIH1-dependent. Co-immunoprecipitation, ubiquitination assays, LC-MS/MS, in vivo xenograft tumor model with ARIH1 manipulation Cellular oncology Low 41123818
2026 Sec61β recruits ARIH1 and 4EHP to the mRNA 5' cap to inhibit eIF4E binding, resulting in selective translational repression of ER-targeted (ERpQC substrate) mRNAs during ER stress; Sec61β deficiency causes cytoplasmic aggresome formation due to overproduction of ERpQC substrates, and motor dysfunction in zebrafish that is rescued by exogenous ARIH1 expression. Co-immunoprecipitation (Sec61β–ARIH1–4EHP complex), mRNA cap-binding assays, Sec61β KD, zebrafish motor behavior rescue by ARIH1 overexpression, proteasome activity assays EMBO reports Medium 41593190

Source papers

Stage 0 corpus · 69 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 461 21532592
1993 ARI 1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii. International journal of antimicrobial agents 176 18611526
2000 Sequence analysis of ARI-1, a novel OXA beta-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92. Antimicrobial agents and chemotherapy 175 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 114 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 66 26291793
2022 The E3 ubiquitin ligase ARIH1 promotes antiviral immunity and autoimmunity by inducing mono-ISGylation and oligomerization of cGAS. Nature communications 60 36217001
2023 ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade. Nature communications 49 37429863
2017 Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1. Structure (London, England : 1993) 48 28552575
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 47 35046545
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 39 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
2022 The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression. Oncogene 31 35102251
2020 Ventilation and laboratory confirmed acute respiratory infection (ARI) rates in college residence halls in College Park, Maryland. Environment international 31 32028176
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
2022 Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter's Transformation. Frontiers in oncology 24 35174095
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 Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. Frontiers in immunology 23 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
2021 Reply to the commentary by Ben-Ari and Delpire: Bumetanide and neonatal seizures: Fiction versus reality. Epilepsia 19 33764535
2019 5-ARI induces autophagy of prostate epithelial cells through suppressing IGF-1 expression in prostate fibroblasts. Cell proliferation 19 30883989
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
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.) 5 41106484
2023 ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62. Virology journal 5 37005687
2025 Molecular epidemiological characterization of human bocavirus (HBoV) in acute respiratory infection (ARI) patients in Yucheng, China. Frontiers in public health 4 40260169
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
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
2026 Single-cell N4-acetylcytidine regulatory landscape identifies ARIH1 as a ferroptosis-suppressive oncogenic driver in lung adenocarcinoma. Respiratory research 0 42169065
2026 Wild barley cytoplasms reduce grain weight plasticity, with environment-dependent cytonuclear epistasis at the ari-e locus. Molecular breeding : new strategies in plant improvement 0 42169809
2026 Varnimcabtagene autoleucel (ARI-0001) in relapsed or refractory mantle cell lymphoma. HemaSphere 0 42256546
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

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