Affinage

STUB1

E3 ubiquitin-protein ligase CHIP · UniProt Q9UNE7

Length
303 aa
Mass
34.9 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 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

STUB1 (CHIP) is a chaperone-associated U-box E3 ubiquitin ligase that couples the HSP70/HSC70 and HSP90 chaperone systems to the ubiquitin-proteasome and autophagy machineries, acting as a central node in protein quality control and the turnover of signaling regulators (PMID:23880665, PMID:29091030). Through its N-terminal TPR domain it engages chaperone-bound clients and competes with cellular membranes for the same surface, allowing it to relocate to membranes during acute stress and act as a proteostasis sensor (PMID:29091030). Its catalytic activity supports multiple ubiquitin linkage types with distinct outcomes: K48-linked chains direct substrates such as BMAL1, YAP1, Sox2/Nanog, and the RNAi factors AGO2/Dicer to proteasomal degradation (PMID:32041778, PMID:31393050, PMID:35675767, PMID:35533808), whereas K63- and K27-linked, non-degradative chains on AHR and the TCR adaptor CARMA1 modulate immune and NF-κB signaling (PMID:35943876, PMID:23322406). STUB1 also drives chaperone-mediated autophagy of HIF1A and selective autophagy of damaged organelles, ubiquitinating stressed peroxisomes for pexophagy and proteasomes for proteaphagy (PMID:23880665, PMID:33077711, PMID:32723828). Through substrate-specific ubiquitination it broadly restrains transcription factors, receptors, and metabolic enzymes—degrading phosphorylated TFEB, the IFNγ-R1/JAK1 complex, IL-4Rα, PKM2, GLUD1, GPX4, and the m6A writer METTL14—thereby tuning autophagy, cytokine signaling, glycolytic and glutamine metabolism, ferroptosis, and RNA modification (PMID:28754656, PMID:35395848, PMID:24251647, PMID:28346425, PMID:37416474, PMID:38110356, PMID:36597993). STUB1 preferentially recognizes pathological phospho-tau via its TPR domain and suppresses tau aggregation and seeding, and heterozygous missense variants in STUB1 cause autosomal dominant ataxia with selective Purkinje cell loss (PMID:37330289, PMID:32211513).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2013 High

    Established that STUB1 functions beyond proteasomal degradation by acting downstream of the chaperone HSPA8 and the CMA receptor LAMP2A to drive lysosomal clearance of a transcription factor, linking the ligase to chaperone-mediated autophagy.

    Evidence Ligase-dead and HSPA8-binding STUB1 mutants with lysosome translocation assays for HIF1A

    PMID:23880665

    Open questions at the time
    • Does not define how STUB1 selects CMA versus proteasomal routing for a given client
    • Generality across other CMA substrates not addressed
  2. 2013 Medium

    Showed STUB1 produces non-degradative ubiquitin chains as a positive signaling input, contrasting its more familiar role as a degradative ligase.

    Evidence Co-IP, RNAi, and K27-linkage-specific ubiquitination of CARMA1 with NF-κB reporter and IL-2 readouts in T cells

    PMID:23322406

    Open questions at the time
    • Specific CARMA1 lysines not mapped
    • Single lab; mechanism of chain-type selection unclear
  3. 2014 Medium

    Defined how HSP70 versus HSP90 differentially gate STUB1 substrate ubiquitination, establishing that the chaperone bound to a client determines whether STUB1 degrades it.

    Evidence Co-IP, geldanamycin HSP90 inhibition, and Smad3 ubiquitination/TGF-β readouts

    PMID:24613385

    Open questions at the time
    • Structural basis of opposing chaperone effects not resolved
    • In vivo relevance not tested
  4. 2017 High

    Connected STUB1 to autophagy and metabolic control by showing it degrades phosphorylated TFEB and the glycolytic enzyme PKM2, positioning the ligase as a regulator of lysosomal biogenesis and the Warburg effect.

    Evidence Co-IP, ubiquitination assays, STUB1 KO cells/mice and KO MEFs with autophagy, mitochondrial, and tumor-growth readouts

    PMID:28346425 PMID:28754656

    Open questions at the time
    • Phospho-dependence recognition mechanism for TFEB not structurally defined
    • Tissue-specific contributions of each substrate unresolved
  5. 2017 High

    Revealed a chaperone-independent, membrane-docking mode in which STUB1 senses proteostasis stress, showing HSP70 and lipid membranes compete for the same TPR surface and that relocated STUB1 fragments the Golgi.

    Evidence In vitro liposome reconstitution, HSP70-versus-membrane competition assay, and live-cell Golgi imaging

    PMID:29091030

    Open questions at the time
    • Physiological triggers and reversibility of membrane docking not fully defined
    • Substrates engaged at membranes not enumerated
  6. 2020 High

    Extended STUB1's quality-control role to whole organelles and the degradation machinery itself, showing chaperone-driven targeting of stressed peroxisomes (pexophagy) and K63-ubiquitination of inhibited proteasomes (proteaphagy).

    Evidence Optogenetic ROS induction with live imaging for pexophagy; in vitro ubiquitination of purified proteasomes and aggresome/autophagy readouts

    PMID:32723828 PMID:33077711

    Open questions at the time
    • Substrate adaptors that mark organelles for STUB1 not fully identified
    • How STUB1 distinguishes damaged from healthy organelles unclear
  7. 2020 High

    Demonstrated stress-induced nuclear relocation of STUB1 to degrade the clock factor BMAL1 via K48 chains, tying the ligase to circadian regulation and oxidative-stress-induced senescence.

    Evidence AP-MS, domain mapping, K48-linkage ubiquitination, nuclear fractionation, and SA-β-gal senescence assays

    PMID:32041778

    Open questions at the time
    • Trigger for nuclear translocation not molecularly defined
    • Circadian phenotype in vivo not tested
  8. 2022 High

    Unbiased CRISPR screens placed STUB1 as a degradative regulator of immune and stemness programs, identifying the IFNγ-R1/JAK1 complex and the pluripotency factors Sox2/Oct4/Nanog as substrates with linkage-specific (K48/K63) outcomes.

    Evidence Genome-wide CRISPR screens, site-specific ubiquitination-site mutagenesis, T-cell killing and reprogramming/differentiation assays

    PMID:35395848 PMID:35675767

    Open questions at the time
    • What determines K48 versus K63 chain choice on different stemness factors is unresolved
    • Interplay between substrates in a single cell type not addressed
  9. 2023 High

    Showed STUB1 preferentially recognizes pathological phospho-tau through a partly distinct TPR-binding mode and suppresses its aggregation and seeding, mechanistically linking the ligase to neurodegeneration-relevant proteostasis.

    Evidence In vitro binding/aggregation/ubiquitination assays with TPR mutagenesis and cell-based seeding assays

    PMID:37330289

    Open questions at the time
    • In vivo tau clearance by STUB1 not tested here
    • Relationship to ataxia-causing TPR variants not directly addressed
  10. 2024 High

    Established STUB1 as a regulator of RNA modification and ferroptosis by degrading the m6A writer METTL14 and the m5C writer NSUN2, with the latter coupling to GPX4 mRNA methylation and hepatocyte ferroptosis.

    Evidence Site-specific ubiquitination-site mutagenesis, m6A/m5C quantification, and in vivo/in vitro ferroptosis models

    PMID:36597993 PMID:39453812

    Open questions at the time
    • How STUB1 access to RNA-modifying enzymes is regulated is unknown
    • Cross-talk between m6A and m5C arms of STUB1 control not defined
  11. 2024 Medium

    Revealed upstream control of STUB1 itself through post-translational modification, with BCKDK phosphorylation at S19 and KAT5 acetylation regulating its activity and abundance, and TRIM6 driving its degradation.

    Evidence Phospho-/acetylation and ubiquitination assays with site-directed mutagenesis and tumor models

    PMID:33728863 PMID:38561411 PMID:38621458

    Open questions at the time
    • Integrated regulatory logic governing STUB1 activity in vivo is unresolved
    • Single-lab findings per modification

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STUB1 integrates substrate recognition, chaperone state, subcellular relocation, and ubiquitin chain-type selection into a coherent decision (degrade versus signal, proteasome versus autophagy) across its very broad substrate set remains unresolved.
  • No unifying structural/biochemical rule for chain-type selection
  • Tissue- and stress-context-specific substrate prioritization not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 9 GO:0140096 catalytic activity, acting on a protein 8 GO:0031386 protein tag activity 4 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0005777 peroxisome 1 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-9612973 Autophagy 5 R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9909396 Circadian clock 1
Partners
CARMA1HSP70HSP90HSPA8JAK1SMAD3TRIM6YTHDF2

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 STUB1, a chaperone-dependent E3 ubiquitin ligase, preferentially interacts with and ubiquitinates phosphorylated (inactive) TFEB, targeting it for proteasomal degradation. STUB1 deficiency leads to accumulation of phosphorylated TFEB and reduced TFEB transcriptional activity, reduced autophagy, and reduced mitochondrial biogenesis. Immunoprecipitation, immunoblot, STUB1 knockout cells and STUB1-deficient mice, overexpression studies The EMBO journal High 28754656
2013 STUB1 is required for degradation of HIF1A by chaperone-mediated autophagy (CMA). STUB1 mutations that abolish either E3 ubiquitin ligase activity or HSPA8-binding prevent HIF1A lysosomal degradation. STUB1 functions downstream of HSPA8 and the CMA receptor LAMP2A to mediate HIF1A ubiquitination and translocation into lysosomes. Mutagenesis of STUB1 (ligase-dead and HSPA8-binding mutants), lysosome isolation/translocation assay, immunoprecipitation, immunoblot Autophagy High 23880665
2014 STUB1 interacts with IL-4Rα and targets it for ubiquitination-mediated proteasomal degradation, terminating IL-4/IL-13 signaling. STUB1 knockout cells show increased IL-4Rα levels and sustained STAT6 activation; STUB1-deficient mice exhibit spontaneous airway inflammation, M2 macrophage activation, and elevated serum IgE. Co-immunoprecipitation, immunoblot, flow cytometry, STUB1 KO mouse model, in vivo lung inflammation measurements American journal of respiratory and critical care medicine High 24251647
2013 CHIP/STUB1 negatively regulates NF-κB signaling in colorectal cancer cells by promoting ubiquitination and proteasomal degradation of p65, a NF-κB subunit, leading to decreased expression of NF-κB target oncogenes (Cyclin D1, c-Myc, MMP-2, VEGF, IL-8). Overexpression and RNAi knockdown in HCT-116 cells, ubiquitination assay, nude mouse tumor growth assay, immunoblot Carcinogenesis Medium 24302614
2017 CHIP/STUB1 (U-box E3 ligase) suppresses the Warburg effect in ovarian carcinoma by interacting with and mediating ubiquitin-proteasomal degradation of pyruvate kinase isoenzyme M2 (PKM2), thereby regulating glycolytic metabolism. SiLAD proteomics, Co-IP, ubiquitination assay, CHIP KO MEF cells, in vitro and in vivo tumor growth assays Oncogene High 28346425
2020 STUB1 specifically ubiquitinates purified human proteasomes in vitro, mainly via Lys63-linked chains. Inhibited proteasomes are sequestered into aggresomes via HDAC6- and dynein-mediated transport and cleared through selective macroautophagy (proteaphagy); STUB1 activity is required for this proteasome quality-control pathway. In vitro ubiquitination assay with purified proteasomes, genetic and chemical inhibition of STUB1, live imaging, colocalization with SQSTM1/HDAC6 Proceedings of the National Academy of Sciences of the United States of America High 32723828
2020 STUB1 promotes ubiquitination of BMAL1 via Lys-48-linked polyubiquitin chains, leading to its proteasomal degradation. Oxidative stress promotes STUB1 nuclear translocation and co-localization with BMAL1. STUB1-mediated BMAL1 degradation attenuates hydrogen peroxide-induced cell senescence. Affinity purification-MS, Co-IP, domain mapping, ubiquitination assay, proteasome inhibition, nuclear fractionation/localization, senescence-associated β-gal staining The Journal of biological chemistry High 32041778
2022 STUB1 is an E3 ubiquitin ligase for the IFNγ receptor subunit IFNγ-R1 in complex with JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of the IFNγ-R1/JAK1 complex through specific lysine residues IFNγ-R1K285 and JAK1K249, thereby suppressing tumor IFNγ signaling. Genome-wide CRISPR/Cas9 screen, Co-IP, ubiquitination assay, site-directed mutagenesis of ubiquitination sites, cytotoxic T-cell killing assay Nature communications High 35395848
2020 Hsc70 mediates translocation of STUB1 onto oxidatively stressed peroxisomes, promoting their selective ubiquitination and autophagic degradation (pexophagy). Artificially targeting STUB1 to healthy peroxisomes is sufficient to trigger pexophagy. STUB1 ataxia patient mutants are defective in pexophagy induction. Live-cell imaging with optogenetic ROS induction, confocal microscopy, Stub1 targeting assay, patient mutant analysis, immunofluorescence Nature communications High 33077711
2013 STUB1 constitutively interacts with the adaptor protein CARMA1, with interaction intensified by TCR stimulation. STUB1 ubiquitinates CARMA1 via Lys-27-linked chains, which is required for TCR-induced canonical NF-κB activation and IL-2 production. STUB1 knockdown abolishes endogenous CARMA1 ubiquitination and NF-κB activation downstream of TCR. Co-immunoprecipitation, RNAi knockdown, overexpression, ubiquitin linkage-specific analysis, NF-κB reporter assay, IL-2 measurement European journal of immunology Medium 23322406
2014 Hsp70 and Hsp90 oppositely regulate CHIP/STUB1-mediated ubiquitination and degradation of Smad3. Overexpressed Hsp70 or Hsp90 inhibition (by geldanamycin) facilitates CHIP-induced Smad3 ubiquitination and degradation (enhancing TGF-β signaling sensitivity), while overexpressed Hsp90 antagonizes CHIP-mediated Smad3 ubiquitination (desensitizing TGF-β signaling). Co-immunoprecipitation, overexpression, pharmacological Hsp90 inhibition, ubiquitination assay, TGF-β signaling readouts Biochemical and biophysical research communications Medium 24613385
2019 STUB1 ubiquitinates YAP1 at K280 via K48-linked polyubiquitination, promoting YAP1 proteasomal degradation and inhibiting cancer cell survival and chemoresistance in gastric cancer. Co-IP, ubiquitination assay, site-directed mutagenesis (K280), immunoblot, cell viability assays Cancer science Medium 31393050
2017 STUB1 binds to RUNX1 and induces its ubiquitination and proteasomal degradation, primarily in the nucleus, and also promotes nuclear export of RUNX1. STUB1 similarly ubiquitinates the leukemogenic fusion RUNX1-RUNX1T1. Overexpression of STUB1 inhibits growth of myeloid leukemia cells harboring RUNX1-RUNX1T1. High-throughput binding assay, Co-IP, ubiquitination assay, immunofluorescence for nuclear/cytoplasmic localization, cell growth assays The Journal of biological chemistry Medium 28536267
2023 CHIP/STUB1 binds ~10-fold more strongly to phosphorylated tau than unmodified tau via its TPR domain (partially distinct from canonical binding mode). Sub-stoichiometric CHIP strongly suppresses aggregation and seeding of phosphorylated tau and promotes rapid ubiquitination of phosphorylated (but not unmodified) tau in vitro. In cells, CHIP restricts seeding by phosphorylated tau. In vitro binding assay (panel of TPR-domain proteins), aggregation assay, in vitro ubiquitination assay, TPR domain mutagenesis, cell-based seeding assay Journal of molecular biology High 37330289
2023 HSP90β inhibits STUB1-induced ubiquitination and degradation of YTHDF2 in the cytoplasm of hepatocellular carcinoma cells. The large and small middle domain of HSP90β is required for its interaction with both STUB1 and YTHDF2. STUB1 directly interacts with YTHDF2 to promote its ubiquitination-mediated proteasomal degradation. Co-immunoprecipitation, domain deletion mapping, ubiquitination assay, overexpression and knockdown, immunoblot Advanced science Medium 37515378
2023 STUB1 is the E3 ubiquitin ligase for METTL14, directly interacting with it and mediating its ubiquitination at K148, K156, and K162 for proteasomal degradation. METTL3 competitively protects METTL14 from STUB1-mediated degradation via METTL3 amino acid regions 450-454 and 464-480, thereby maintaining m6A homeostasis. Co-IP, ubiquitination assay, site-directed mutagenesis of ubiquitination sites, domain mapping of METTL3, m6A quantification, immunoblot EMBO reports High 36597993
2020 PDLIM5 interacts with SMAD3 (but not SMAD2) and competitively suppresses the interaction between SMAD3 and its E3 ubiquitin ligase STUB1, protecting SMAD3 from STUB1-mediated proteasomal degradation and maintaining TGF-β signaling in NSCLC cells. Co-IP, knockdown/overexpression, ubiquitination assay, immunoblot, rescue experiments The Journal of biological chemistry Medium 32737199
2022 STUB1 promotes K63-linked non-degradative ubiquitination of aryl hydrocarbon receptor (AHR), facilitating Th17/Treg cell imbalance in rheumatoid arthritis. Specific ubiquitination sites on AHR were identified as responsible for STUB1-mediated K63 ubiquitination. Western blot, flow cytometry, siRNA knockdown, EROD enzymatic activity assay, ubiquitination assay with linkage-specific analysis Clinical and experimental immunology Medium 35943876
2022 STUB1 promotes K48-linked polyubiquitination of AGO2 and Dicer (including aviDicer), targeting them for proteasomal degradation in a chaperone-dependent manner. STUB1 also induces degradation of AGO1, AGO3, and AGO4. STUB1 deficiency upregulates Dicer and AGO2, enhancing antiviral RNAi and inhibiting viral replication in mammalian cells and newborn mouse models. Co-IP, ubiquitination assay with K48-linkage analysis, overexpression/knockdown, in vivo newborn mouse model with virus-derived siRNA measurement Virologica Sinica Medium 35533808
2017 CHIP/STUB1, when freed from chaperones during acute stress, docks on cellular membranes (phosphatidic acid and phosphatidylinositol-4-phosphate enhance association), performing a proteostasis sensor function. HSP70 and membranes compete for mutually exclusive binding to the TPR domain of CHIP. At new cellular locations, CHIP participates in Golgi apparatus fragmentation. In vitro reconstitution with liposomes, competition assay (HSP70 vs. membrane), cellular imaging of Golgi fragmentation, lipid binding assays eLife High 29091030
2015 CHIP/STUB1 knockdown increases PTEN protein levels and decreases AKT/mTOR activity and ULK1 Ser757 phosphorylation, promoting autophagosome formation. However, CHIP knockdown also disturbs autophagic flux (impairs p62 substrate degradation) and increases susceptibility to autophagic cell death induced by bafilomycin A1. RNAi knockdown, immunoblot for autophagy pathway components (PTEN, AKT, mTOR, ULK1, p62), bafilomycin A1 treatment, cell death assay Neuroscience bulletin Medium 26219223
2022 The E3 ubiquitin ligase STUB1 mediates ubiquitination and proteasomal degradation of Sox2 and Nanog via K48-linked chains, and Oct4 via K63-linked chains. STUB1 deficiency enhances somatic cell reprogramming and delays ESC differentiation, while enforced STUB1 expression triggers ESC differentiation. CRISPR-Cas9 KO library screen, Co-IP, K48/K63 linkage-specific ubiquitination assays, protein half-life measurement, reprogramming and differentiation assays Cell reports High 35675767
2020 STUB1 deficiency leads to intracellular accumulation of protein aggregates and increased secretion of small extracellular vesicles (exosomes) enriched in ubiquitinated and/or undegraded proteins and oligomers. Oxidative stress augments sEV release in STUB1-depleted cells, indicating that STUB1 and exosomes cooperate to maintain proteostasis. STUB1 KO/knockdown, nanoparticle tracking analysis of sEVs, immunoblot for ubiquitinated proteins in sEVs, oxidative stress treatment PloS one Medium 31613922
2023 Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated ubiquitination of GPX4 at site K191, leading to GPX4 degradation. STUB1 knockdown or GPX4 overexpression reverses imatinib-induced ferroptosis. Co-IP, ubiquitination assay with site-directed mutagenesis (K191), GPX4 knockdown/overexpression, ferroptosis markers (lipid ROS, Fe2+, GSH), in vivo xenograft Cell death & disease Medium 38110356
2024 STUB1 mediates ubiquitination of NSUN2 at lysines K457 and K654, promoting NSUN2 proteasomal degradation during ferroptosis. NSUN2 degradation diminishes m5C methylation of Gpx4 mRNA 3' UTR, reducing GPX4 protein expression and promoting hepatocyte ferroptosis. Co-IP, ubiquitination assay with site-specific mutagenesis, m5C methylation assay, SECIS-SBP2 interaction assay, NSUN2 knockdown/overexpression, in vivo and in vitro ferroptosis models Cell reports High 39453812
2023 STUB1 mediates ubiquitination and proteasomal degradation of GLUD1 at lysine K503, regulating glutamine catabolism in lung adenocarcinoma. Inhibition of K503 ubiquitination promotes proliferation and tumor growth. Co-IP, ubiquitination assay, site-directed mutagenesis (K503), cell proliferation assay, in vivo tumor growth iScience Medium 37416474
2021 CHIP/STUB1 targets newly synthesized, HSP90/HSC70-associated ErbB2 for ubiquitin/proteasome-dependent degradation in the endoplasmic reticulum and Golgi, establishing a mechanism for negative regulation of cell surface ErbB2 levels in breast cancer cells. STUB1 knockdown and overexpression, proteasome inhibition, ER/Golgi fractionation, immunoblot, ErbB2 surface expression measurement Cancers Medium 34439093
2014 CHIP/STUB1 directly interacts with eIF5A preferentially through its U-box domain, mediating eIF5A ubiquitination and proteasomal degradation. CHIP expression inversely correlates with eIF5A levels in colorectal cancers and in CHIP KO MEF cells. Proteomics identification, Co-IP, domain mapping (U-box), ubiquitination assay, CHIP KO MEF cells, immunoblot Cellular signalling Medium 24509416
2020 STUB1 is targeted by the SUMO-interacting motif SIM3 of EBV EBNA1. The SIM3 motif mediates EBNA1's inhibitory effects on SUMO2-modified STUB1 and regulates SUMO2-mediated degradation of USP7. Hypoxic stress induces dissociation of EBNA1 from STUB1, increasing SUMO1 modification of STUB1 and KAP1 to promote lytic reactivation. Proteomic analysis, Co-IP, mutagenesis of SIM motifs, ubiquitination/SUMOylation assays, viral replication assays PLoS pathogens Medium 32176739
2024 BCKDK phosphorylates STUB1 at S19, disrupting the STUB1-BCAT1 interaction and inhibiting STUB1-mediated ubiquitination and degradation of BCAT1, thereby stabilizing BCAT1 in glioblastoma. Co-IP, phosphorylation assay, ubiquitination assay, site-directed mutagenesis, in vivo and in vitro tumor models Cancer letters Medium 38621458
2024 STUB1 is acetylated by KAT5 (lysine acetyltransferase 5), and KAT5 promotes STUB1 transcription via acetylation modulation. STUB1 then ubiquitinates and promotes degradation of LATS2, activating the YAP/β-catenin pathway and inhibiting NLRP3-mediated cardiomyocyte pyroptosis during myocardial ischemia-reperfusion injury. Acetylation assay, ubiquitination assay, KAT5/STUB1 overexpression/knockdown, LATS2 stability assay, pyroptosis markers, in vivo MIRI model Communications biology Medium 38561411
2023 Salidroside increases STUB1 expression in Tregs and promotes STUB1-mediated degradation of Foxp3 in the nucleus, suppressing Treg function. Hsp70 is required for the colocalization of STUB1 and Foxp3 in the nucleus; Hsp70 inhibition reverses SAL-induced suppression of Foxp3 and disrupts the STUB1-Foxp3 colocalization. Flow cytometry, confocal laser microscopy for nuclear colocalization, Hsp70 inhibitor treatment, network pharmacology and molecular docking BMC cancer Low 37528345
2020 Heterozygous missense variants in STUB1 (p.Ile53Thr and p.Thr37Leu) cause autosomal dominant ataxia. Neuropathological examination reveals selective Purkinje cell loss and aberrant STUB1 localization in distal Purkinje cell dendritic arbors (loss of normal somatodendritic polarization), linking STUB1 mislocalization to cerebellar pathogenesis. Exome sequencing, neuropathological examination, immunofluorescence localization of STUB1 in post-mortem brain tissue Neurology. Genetics Medium 32211513
2023 STUB1 mediates ubiquitination of HOXB3, inhibiting its expression; loss of HOXB3 reduces PARK7 transcription (as HOXB3 binds PARK7 promoter), thereby promoting ferroptosis and suppressing paclitaxel resistance in ovarian cancer. Co-IP, dual luciferase reporter assay, ubiquitination assay, ChIP for HOXB3 binding to PARK7 promoter, in vivo xenograft Communications biology Medium 39501077
2023 STUB1 ubiquitinates and promotes degradation of SMYD2 in glioma cells treated with cisplatin; STUB1 knockdown reverses cisplatin-induced SMYD2 degradation and partially restores cell function. UbiBrowser prediction confirmed by knockdown, ubiquitination assay, Co-IP, cell functional assays Journal of molecular neuroscience Low 35939202
2023 Allosteric inhibition of HSP70 (by JG98/JG231) promotes STUB1 nuclear translocation to bind and degrade AR-V7 in enzalutamide-resistant prostate cancer cells. STUB1 knockdown diminishes the anticancer effects and partially restores AR-V7 levels, indicating that HSP70/STUB1 machinery regulates AR/AR-V7 protein stability. STUB1 knockdown, nuclear fractionation/localization, Co-IP, immunoblot, cell growth assays, in vivo xenograft Pharmacological research Medium 36773708
2021 TRIM6 interacts with STUB1 and promotes ubiquitination-mediated proteasomal degradation of STUB1, leading to increased YAP1 protein levels and enhanced breast cancer progression. Co-IP, ubiquitination assay, TRIM6 overexpression/knockdown, YAP1 protein level measurements, in vitro and in vivo cancer growth assays European journal of histochemistry Medium 33728863

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Organoids-on-a-chip. Science (New York, N.Y.) 610 31171693
2003 Protein chip technology. Current opinion in chemical biology 597 12547427
2005 Blood-on-a-chip. Annual review of biomedical engineering 364 16004567
2017 The Exosome Total Isolation Chip. ACS nano 302 29090896
2021 Clonal hematopoiesis of indeterminate potential (CHIP): Linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease. Journal of molecular and cellular cardiology 222 34298011
2017 STUB1 regulates TFEB-induced autophagy-lysosome pathway. The EMBO journal 199 28754656
2002 How to make a DNA chip. Angewandte Chemie (International ed. in English) 167 19750752
2014 Platelet bioreactor-on-a-chip. Blood 162 25606631
2013 STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy. Autophagy 156 23880665
2020 Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip. Micromachines 125 32570945
2014 ChIP-Enrich: gene set enrichment testing for ChIP-seq data. Nucleic acids research 118 24878920
2009 Genomic location analysis by ChIP-Seq. Journal of cellular biochemistry 118 19173299
2008 Current development in microfluidic immunosensing chip. Analytica chimica acta 114 18298963
2011 ChIP-chip versus ChIP-seq: lessons for experimental design and data analysis. BMC genomics 95 21356108
2006 ChIP-chip comes of age for genome-wide functional analysis. Cancer research 92 16849531
2002 On-chip enzymatic assays. Electrophoresis 86 11891703
2018 Simplified ChIP-exo assays. Nature communications 82 30030442
2013 CHIP/Stub1 functions as a tumor suppressor and represses NF-κB-mediated signaling in colorectal cancer. Carcinogenesis 81 24302614
2020 AI on a chip. Lab on a chip 80 32644061
2015 Controlled electromechanical cell stimulation on-a-chip. Scientific reports 80 26135970
1999 DNA chip technology. The Journal of pathology 74 10398077
2019 Latest Trends in Biosensing for Microphysiological Organs-on-a-Chip and Body-on-a-Chip Systems. Biosensors 66 31546916
2017 CHIP/Stub1 regulates the Warburg effect by promoting degradation of PKM2 in ovarian carcinoma. Oncogene 66 28346425
2013 On-chip biomedical imaging. IEEE reviews in biomedical engineering 65 23558399
2008 Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2. Proceedings of the National Academy of Sciences of the United States of America 62 18682557
2023 HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 58 37515378
2011 RIP-Chip analysis: RNA-Binding Protein Immunoprecipitation-Microarray (Chip) Profiling. Methods in molecular biology (Clifton, N.J.) 57 21125495
2014 Regulation of IL-4 receptor signaling by STUB1 in lung inflammation. American journal of respiratory and critical care medicine 55 24251647
2020 The E3 ubiquitin ligase STUB1 attenuates cell senescence by promoting the ubiquitination and degradation of the core circadian regulator BMAL1. The Journal of biological chemistry 53 32041778
2020 Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes. Proceedings of the National Academy of Sciences of the United States of America 53 32723828
2014 Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. Orphanet journal of rare diseases 52 24742043
2022 Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress tumor IFNγ signaling. Nature communications 50 35395848
2020 PDLIM5 inhibits STUB1-mediated degradation of SMAD3 and promotes the migration and invasion of lung cancer cells. The Journal of biological chemistry 50 32737199
2018 ChIP-Quantitative Polymerase Chain Reaction (ChIP-qPCR). Cold Spring Harbor protocols 49 29717044
2007 ChIP-chip: data, model, and analysis. Biometrics 48 17825010
2023 Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated GPX4 ubiquitination. Cell death & disease 47 38110356
2019 On-chip crystallization for serial crystallography experiments and on-chip ligand-binding studies. IUCrJ 45 31316815
2014 Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1. Biochemical and biophysical research communications 44 24613385
2023 STUB1/CHIP: New insights in cancer and immunity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 37506582
2018 Construction of integrated gene logic-chip. Nature nanotechnology 41 30038365
2023 METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6 A homeostasis. EMBO reports 40 36597993
2020 Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes. Nature communications 39 33077711
2007 Normalization and experimental design for ChIP-chip data. BMC bioinformatics 39 17592629
2013 STUB1 is essential for T-cell activation by ubiquitinating CARMA1. European journal of immunology 38 23322406
2012 miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 22407479
1999 DNA chip technology ante portas. Journal of molecular medicine (Berlin, Germany) 37 10619436
2019 STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling. Cancer science 36 31393050
2013 Diverse roles of C-terminal Hsp70-interacting protein (CHIP) in tumorigenesis. Journal of cancer research and clinical oncology 34 24370685
2011 Using CisGenome to analyze ChIP-chip and ChIP-seq data. Current protocols in bioinformatics 34 21400695
2015 Defining bacterial regulons using ChIP-seq. Methods (San Diego, Calif.) 33 26032817
2021 Oncoimmunology Meets Organs-on-Chip. Frontiers in molecular biosciences 31 33842539
2021 ChIP-R: Assembling reproducible sets of ChIP-seq and ATAC-seq peaks from multiple replicates. Genomics 31 33878366
2015 Regulation of autophagic flux by CHIP. Neuroscience bulletin 29 26219223
2023 The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT). Journal of molecular biology 28 37330289
2017 The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1-RUNX1T1. The Journal of biological chemistry 28 28536267
2020 STUB1 is targeted by the SUMO-interacting motif of EBNA1 to maintain Epstein-Barr Virus latency. PLoS pathogens 26 32176739
2006 On-chip protein synthesis for making microarrays. Methods in molecular biology (Clifton, N.J.) 26 16785638
2020 Organs-on-a-Chip. Advances in experimental medicine and biology 25 32285363
2010 β-catenin promoter ChIP-chip reveals potential schizophrenia and bipolar disorder gene network. Journal of neurogenetics 23 20615089
2023 Salidroside regulates tumor microenvironment of non-small cell lung cancer via Hsp70/Stub1/Foxp3 pathway in Tregs. BMC cancer 22 37528345
2020 Heterozygous STUB1 missense variants cause ataxia, cognitive decline, and STUB1 mislocalization. Neurology. Genetics 21 32211513
2020 Clinical and pathologic phenotype of a large family with heterozygous STUB1 mutation. Neurology. Genetics 21 32337344
2010 Temporal ChIP-on-Chip of RNA-Polymerase-II to detect novel gene activation events during photoreceptor maturation. Molecular vision 21 20161818
2020 Unidirectional intercellular communication on a microfluidic chip. Biosensors & bioelectronics 20 33288428
2018 ChIP-re-ChIP: Co-occupancy Analysis by Sequential Chromatin Immunoprecipitation. Methods in molecular biology (Clifton, N.J.) 20 29027168
2015 A ChIP on the shoulder? Chromatin immunoprecipitation and validation strategies for ChIP antibodies. F1000Research 20 26594335
2014 CHIP/Stub1 interacts with eIF5A and mediates its degradation. Cellular signalling 20 24509416
2021 Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1. European journal of histochemistry : EJH 19 33728863
2019 Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis. PloS one 19 31613922
2022 E3 ubiquitin ligases STUB1/CHIP contributes to the Th17/Treg imbalance via the ubiquitination of aryl hydrocarbon receptor in rheumatoid arthritis. Clinical and experimental immunology 18 35943876
2005 Chip devices for miniaturized biotechnology. Applied microbiology and biotechnology 18 16228204
2023 Complex Ataxia-Dementia Phenotype in Patients with Digenic TBP/STUB1 Spinocerebellar Ataxia. Movement disorders : official journal of the Movement Disorder Society 16 36799493
2017 CHIP as a membrane-shuttling proteostasis sensor. eLife 16 29091030
2015 Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm. International journal of molecular sciences 16 25993293
2009 ChIP-on-chip analysis of DNA topoisomerases. Methods in molecular biology (Clifton, N.J.) 16 19763945
2024 STUB1-mediated ubiquitination and degradation of NSUN2 promotes hepatocyte ferroptosis by decreasing m5C methylation of Gpx4 mRNA. Cell reports 15 39453812
2023 Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models. Pharmacological research 15 36773708
2023 STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung adenocarcinoma. iScience 15 37416474
2015 Cells on chip for multiplex screening. Biosensors & bioelectronics 15 25892543
2024 STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-β-catenin axis. Communications biology 14 38561411
2024 Cross-talk between BCKDK-mediated phosphorylation and STUB1-dependent ubiquitination degradation of BCAT1 promotes GBM progression. Cancer letters 14 38621458
2022 STUB1 regulates antiviral RNAi through inducing ubiquitination and degradation of Dicer and AGO2 in mammals. Virologica Sinica 14 35533808
2018 Liver sinusoid on a chip. Methods in cell biology 14 30037457
2014 Chromatin immunoprecipitation for ChIP-chip and ChIP-seq. Methods in molecular biology (Clifton, N.J.) 14 24818935
2022 Stub1 maintains proteostasis of master transcription factors in embryonic stem cells. Cell reports 13 35675767
2021 Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular diseases-an updated systematic review. Journal, genetic engineering & biotechnology 13 34279740
2018 ChIP-seq and ChIP-exo profiling of Pol II, H2A.Z, and H3K4me3 in human K562 cells. Scientific data 13 29509191
2024 STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression. Communications biology 12 39501077
2022 ChIP-AP: an integrated analysis pipeline for unbiased ChIP-seq analysis. Briefings in bioinformatics 12 34965583
2022 The Current State of Chromatin Immunoprecipitation (ChIP) from FFPE Tissues. International journal of molecular sciences 12 35163027
2022 A Severe Dementia Syndrome Caused by Intron Retention and Cryptic Splice Site Activation in STUB1 and Exacerbated by TBP Repeat Expansions. Frontiers in molecular neuroscience 12 35493319
2022 STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells. Journal of molecular neuroscience : MN 12 35939202
2022 Integrated Acoustic Chip for Culturing 3D Cell Arrays. ACS sensors 12 36049227
2021 CHIP/STUB1 Ubiquitin Ligase Functions as a Negative Regulator of ErbB2 by Promoting Its Early Post-Biosynthesis Degradation. Cancers 12 34439093
2018 ChIP and ChIP-Related Techniques: Expanding the Fields of Application and Improving ChIP Performance. Methods in molecular biology (Clifton, N.J.) 12 29027160
2018 ChIP. Cold Spring Harbor protocols 12 29610359
2017 Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines. Journal of visualized experiments : JoVE 12 28654055
2017 ICUS/CCUS/CHIP: basics & beyond. Expert review of hematology 12 28832236
2016 Investigation of Viral and Host Chromatin by ChIP-PCR or ChIP-Seq Analysis. Current protocols in microbiology 12 26855283
2018 ChIP-chip. Cold Spring Harbor protocols 11 29717045

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