Affinage

USP9X

Ubiquitin carboxyl-terminal hydrolase 9X · UniProt Q93008

Length
2554 aa
Mass
290.5 kDa
Annotated
2026-06-11
100 papers in source corpus 59 papers cited in narrative 59 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP9X is a substrate-specific deubiquitinase that opposes ubiquitin-dependent proteasomal degradation of a broad set of regulatory proteins, thereby controlling cell survival, signaling, and cytoskeletal and developmental programs (PMID:20023629, PMID:29346117). Its prototypical mode of action is removal of degradative polyubiquitin chains from short-lived substrates to extend their half-life: it stabilizes the anti-apoptotic protein MCL1 by cleaving Lys48-linked chains to promote cell survival (PMID:20023629), and analogously stabilizes the tumor-suppressor F-box protein FBW7 upstream of c-Myc (PMID:29346117), the DNA-replication checkpoint factor CLASPIN to sustain fork progression and CHK1 activation (PMID:26921344), BRCA1 to support homologous recombination (PMID:31512408), and the translation-initiation factor eIF4A1 to maintain cap-dependent synthesis of pro-oncogenic mRNAs (PMID:29228324). A recurring theme is the stabilization of HECT- and RING-family E3 ligases and of other ubiquitin-pathway enzymes—ITCH, SMURF1, and MARCH7—by antagonizing their auto-ubiquitination (PMID:17038327, PMID:23184937, PMID:18410486). Through these substrates USP9X tunes multiple developmental signaling pathways: it stabilizes LATS1/2 and Angiomotin to restrain YAP/TAZ in the Hippo pathway (PMID:28720576, PMID:27462448), acts as a WWP1-antagonizing rheostat on DVL2 and deubiquitinates BCL9 and β-catenin to direct Wnt signaling (PMID:31340145, PMID:27783990, PMID:31073027), activates Notch via MIB1 (PMID:33547080, PMID:27593927), and supports TGF-β/SMAD4 nuclear retention (PMID:28115363). It assembles and activates mTORC1 and mTORC2 by stabilizing RAPTOR and deubiquitinating RICTOR (PMID:28341829, PMID:33378666). USP9X is also an integral centrosomal and centriolar-satellite component that protects CEP131, PCM1, and NPHP5 to support centrosome biogenesis and cell-cycle–coupled ciliogenesis (PMID:28361952, PMID:28498859, PMID:30584065), and is required in neurons for axon growth, migration, and dendritic spine maintenance, partly through stabilization of ankyrin-G (PMID:24607389, PMID:23861879, PMID:31813652); loss-of-function human variants that fail to rescue axonal defects link USP9X to intellectual disability (PMID:24607389). Its catalytic output is gated by post-translational modification, including CDK1-dependent phosphorylation at Ser2563 (antagonized by CDC14B) that licenses mitotic deubiquitination of WT1 (PMID:32152317), S-nitrosylation that enables MIB1 stabilization and NOTCH1 signaling (PMID:33547080), TCR-dependent phosphorylation that enhances activity toward ZAP70 (PMID:26936881), and arginine methylation that recruits TDRD3 to direct stress-granule localization (PMID:28101374).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2006 High

    Established that USP9X protects E3 ubiquitin ligases from auto-ubiquitination, revealing a recurring strategy of stabilizing ubiquitin-pathway enzymes rather than only their downstream targets.

    Evidence GST pulldown, reciprocal co-IP, and RNAi rescue with proteasome inhibitor showing FAM/USP9X binds ITCH WW domains and reverses its auto-ubiquitination

    PMID:17038327

    Open questions at the time
    • Chain topology removed from ITCH not defined
    • Catalytic-dead controls not used in this study
  2. 2008 High

    Showed USP9X removes atypical Lys29/Lys33 chains and that these non-degradative chains regulate kinase activity, broadening USP9X chain specificity beyond canonical degradation signals.

    Evidence In vitro deubiquitinase assay, chain topology analysis, and mutagenesis on NUAK1 and MARK4

    PMID:18254724

    Open questions at the time
    • Direct demonstration that polyubiquitination inhibits T-loop phosphorylation remains inferential
    • In vivo relevance not established
  3. 2009 High

    Identified USP9X as a stabilizer of the anti-apoptotic protein MCL1 via Lys48-chain removal, defining its central pro-survival role and oncogenic relevance.

    Evidence Co-IP, ubiquitination assays, and RNAi knockdown with survival readouts in cancer cells

    PMID:20023629

    Open questions at the time
    • Structural basis of MCL1 recognition not resolved
    • Regulation of the USP9X-MCL1 interaction not addressed here
  4. 2009 High

    Demonstrated USP9X stabilizes activated ASK1 to sustain oxidative-stress JNK signaling, extending its survival/death control into stress kinase pathways via a ubiquitin-like recognition motif.

    Evidence Co-IP, binding-domain mutagenesis of the ASK1 LRLRGG sequence, and JNK/cell-death assays in USP9X-deficient cells

    PMID:20005844

    Open questions at the time
    • Chain type removed from ASK1 not defined
    • Whether the GG motif is a general USP9X docking site untested
  5. 2011 High

    Linked USP9X to neurodegeneration-relevant proteostasis by showing it removes SIAH-added monoubiquitin from α-synuclein and routes it toward autophagy versus proteasome.

    Evidence Deubiquitinase assays, RNAi/overexpression, and cell fractionation distinguishing degradation routes

    PMID:22065755

    Open questions at the time
    • In vivo brain relevance not tested
    • Mechanism of degradation-route selection unresolved
  6. 2013 High

    Defined USP9X as a regulator of neural development, showing conditional loss disrupts cortical organization and axonogenesis partly through impaired TGF-β signaling.

    Evidence Nestin-cre and Emx1-cre conditional knockouts with in vivo/in vitro axon-length and TGF-β analyses

    PMID:23861879

    Open questions at the time
    • Direct deubiquitination substrate driving axon phenotype not identified
    • TGF-β linkage correlative
  7. 2013 High

    Placed USP9X in adaptive immunity by showing it deubiquitinates Bcl10 to enable CBM-complex assembly and NF-κB activation downstream of the TCR.

    Evidence Co-IP, RNAi in T-cell lines and primary T cells, and adoptive-transfer immunization

    PMID:23690623

    Open questions at the time
    • Chain type on Bcl10 not fully defined
    • Direct vs scaffold role within CBM not separated
  8. 2014 High

    Provided causal disease evidence by demonstrating that intellectual-disability–associated USP9X variants fail to rescue axon growth and growth-cone localization in Usp9x-null neurons.

    Evidence Usp9x knockout mouse with human wild-type and variant rescue, axon/migration assays, and proteomics of null neurons

    PMID:24607389

    Open questions at the time
    • Molecular substrate underlying growth-cone defect not pinpointed
    • Genotype-phenotype mechanism for each variant incomplete
  9. 2016 High

    Revealed substrate-directed, signal-activated catalysis by showing TCR phosphorylation enhances USP9X activity toward ZAP70 and that USP9X controls B-cell receptor signaling.

    Evidence Usp9X knockout mouse, ubiquitination and kinase-activity assays, and endosomal localization analysis

    PMID:26936881

    Open questions at the time
    • Kinase phosphorylating USP9X not identified here
    • ZAP70 ubiquitination site not mapped
  10. 2017 High

    Consolidated USP9X as a Hippo-pathway regulator by demonstrating it stabilizes LATS1/2 and Angiomotin to restrain YAP/TAZ-driven oncogenesis and EMT.

    Evidence Co-IP, gel filtration, MEF knockout, site-specific deubiquitination (AMOT K496), and YAP/TAZ reporter/soft-agar assays

    PMID:27462448 PMID:28720576 PMID:29183995

    Open questions at the time
    • Whether USP9X acts on multiple Hippo nodes simultaneously in vivo unclear
    • Some node studies single-lab
  11. 2017 High

    Established USP9X as an integral centrosome and centriolar-satellite component that stabilizes CEP131, PCM1, CEP55, and NPHP5 to control centrosome biogenesis and cell-cycle–coupled ciliogenesis.

    Evidence Co-IP, deubiquitinase assays, centrosome localization microscopy, cell-cycle synchronization, and MIB1-epistasis ciliogenesis assays

    PMID:28361952 PMID:28498859 PMID:28620049 PMID:30584065 PMID:31671755

    Open questions at the time
    • Recruitment hierarchy among satellite partners incompletely ordered
    • Some interactions (CEP55, SNX17) Medium-confidence single-lab
  12. 2018 High

    Demonstrated tumor-suppressive control of FBW7 and downstream c-Myc in vivo, showing USP9X stabilizes an E3 ligase to restrain proliferation and tumorigenesis.

    Evidence Conditional gut knockout, proteomics, organoids, and genetic epistasis with c-Myc heterozygosity

    PMID:29346117

    Open questions at the time
    • Chain type removed from FBW7 not defined
    • Tissue specificity of the FBW7-c-Myc axis untested elsewhere
  13. 2019 High

    Defined USP9X as a Wnt-pathway rheostat by showing it antagonizes WWP1 on DVL2 and deubiquitinates BCL9 to specify canonical versus PCP outcomes and potentiate β-catenin transcription.

    Evidence Deubiquitination assays, WNT/PCP reporters, site-specific ubiquitination mapping (BCL9 K212), and ChIP

    PMID:31073027 PMID:31340145

    Open questions at the time
    • Quantitative rules of the WWP1-USP9X balance unresolved
    • BCL9 study Medium-confidence single-lab
  14. 2019 High

    Connected USP9X to neuronal cytoskeletal scaffolding by showing phosphorylation-enhanced deubiquitination of ankyrin-G maintains dendritic spine density into adulthood.

    Evidence Forebrain-specific conditional knockout, ubiquitination assays, phosphorylation analysis, and spine-density measurement

    PMID:31813652

    Open questions at the time
    • Kinase responsible for the activating phosphorylation not identified
    • Transient versus persistent substrate effects not fully explained
  15. 2020 High

    Defined the mitotic activation switch by showing CDK1 phosphorylates USP9X at Ser2563 (reversed by CDC14B) to license deubiquitination and stabilization of the mitotic transcription factor WT1.

    Evidence Proteome-wide phosphorylation screening, in vitro phosphorylation, deubiquitination assays, and CXCL8 reporter assay

    PMID:32152317

    Open questions at the time
    • Full substrate set gated by Ser2563 phosphorylation unknown
    • Structural impact of the modification unresolved
  16. 2020 High

    Showed USP9X assembles mTORC2 by removing Lys63 chains from RICTOR to promote mTOR association, complementing earlier RAPTOR/mTORC1 stabilization and placing USP9X in growth-factor mTOR control.

    Evidence Co-IP, chain-type analysis, mTORC2 kinase assays in cells and mice

    PMID:22544753 PMID:28341829 PMID:33378666

    Open questions at the time
    • How USP9X coordinately balances mTORC1 vs mTORC2 unclear
    • RAPTOR ubiquitination site not mapped
  17. 2021 High

    Identified S-nitrosylation as a redox-sensitive regulatory switch enabling USP9X to stabilize MIB1 and drive NOTCH1 signaling, with in vivo relevance to aortic valve disease.

    Evidence Unbiased S-nitrosylation proteomics, mouse knockout, scRNA-seq, and in vitro deubiquitination

    PMID:33547080

    Open questions at the time
    • S-nitrosylated residues not enumerated mechanistically
    • Generality of redox gating across substrates untested
  18. 2021 High

    Extended USP9X function to translational quality control by showing it stabilizes the RQC E3 ligases Makorin 2 and ZNF598 to sustain ribosomal stalling responses.

    Evidence Validated small-molecule USP9X inhibitor, proteomics, co-IP, and ribosomal-stalling assays

    PMID:33507233

    Open questions at the time
    • Direct deubiquitination of these ligases versus indirect effects not fully separated
    • Physiological RQC consequences in vivo untested
  19. 2022 High

    Demonstrated in vivo metabolic-disease relevance by showing USP9X removes Lys63 chains from a defined site on scavenger receptor SR-A1 to limit ox-LDL uptake and foam-cell formation.

    Evidence Loss-of-function screen, site-specific K27R mutagenesis, chain typing, and macrophage-specific knockout mouse

    PMID:35389885

    Open questions at the time
    • Whether SR-A1 regulation generalizes to other scavenger receptors unknown
    • Upstream signal controlling this activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how USP9X achieves substrate selectivity across its very broad substrate range and how its multiple regulatory modifications are integrated to direct activity toward specific substrates in a given context.
  • No structural model of substrate or chain-type recognition
  • No systematic map linking each PTM (phosphorylation, S-nitrosylation, methylation) to specific substrate pools
  • Adaptor-driven recruitment (e.g., SNX17, TDRD3, NPHP5) not generalized into a recruitment code

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 5 GO:0016787 hydrolase activity 4
Localization
GO:0005815 microtubule organizing center 4 GO:0005829 cytosol 3 GO:0005929 cilium 3 GO:0005768 endosome 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
CLASPINDVL2FBW7ITCHMCL1MIB1PCM1SMURF1
Complex memberships
CARMA1-BCL10-MALT1 (CBM) complexcentrosome / centriolar satellitesmTORC1mTORC2

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 USP9X binds MCL1 and removes Lys48-linked polyubiquitin chains from MCL1, preventing its proteasomal degradation and thereby stabilizing MCL1 to promote cell survival. Knockdown of USP9X increases MCL1 polyubiquitination and enhances MCL1 turnover. Co-immunoprecipitation, ubiquitination assays, RNAi knockdown, cell survival assays Nature High 20023629
2008 USP9X interacts with and deubiquitinates AMPK-related kinases NUAK1 and MARK4, removing atypical Lys29/Lys33-linked polyubiquitin chains. Non-USP9X-binding mutants of NUAK1 and MARK4 are hyper-ubiquitinated and lack LKB1-mediated T-loop phosphorylation, suggesting polyubiquitination inhibits these kinases. Co-immunoprecipitation, in vitro deubiquitinase assay, ubiquitin chain topology analysis, mutagenesis, overexpression/knockdown The Biochemical journal High 18254724
2010 USP9X mediates selective autophagy (zymophagy) of activated zymogen granules in pancreatic acinar cells by interacting with the autophagy protein VMP1 and the ubiquitin-binding protein p62, forming a VMP1-USP9X-p62 pathway required for selective autophagosome formation. Co-immunoprecipitation, cellular/biochemical characterization, genetically engineered mice, cultured acinar cells The Journal of biological chemistry Medium 21173155
2011 USP9X interacts with and deubiquitinates α-synuclein, removing monoubiquitin added by SIAH. Deubiquitinated α-synuclein is preferentially degraded by autophagy, while monoubiquitinated α-synuclein is preferentially degraded by the proteasome. USP9X knockdown promotes accumulation of monoubiquitinated α-synuclein and toxic inclusions. Co-immunoprecipitation, deubiquitinase activity assay, RNAi knockdown, USP9X overexpression, cell fractionation Proceedings of the National Academy of Sciences of the United States of America High 22065755
2009 USP9X binds ASK1 via a ubiquitin-like GG sequence (LRLRGG) in ASK1's C-terminus and stabilizes activated ASK1 by preventing its ubiquitin-dependent degradation. USP9X-deficient cells show reduced oxidative stress-induced JNK activation and cell death. Co-immunoprecipitation, binding domain mutagenesis, USP9X-deficient cells, JNK activation assay, cell death assay Molecular cell High 20005844
2006 FAM/USP9X binds the ITCH ubiquitin ligase via ITCH's WW domains, deubiquitinates auto-ubiquitinated ITCH, and protects it from proteasomal degradation. RNAi depletion of FAM/USP9X reduces endogenous ITCH levels, rescued by proteasome inhibitor. GST pulldown, co-immunoprecipitation, co-localization, RNAi knockdown, overexpression The Journal of biological chemistry High 17038327
2012 FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 through the second WW domain of SMURF1 and the C-terminus of USP9X. USP9X antagonizes SMURF1 auto-ubiquitination and proteasomal degradation, thereby stabilizing SMURF1. Depletion of USP9X reduces SMURF1 levels and impairs cell migration in MDA-MB-231 breast cancer cells. Quantitative mass spectrometry, co-immunoprecipitation, domain mapping, deubiquitination assay, RNAi knockdown, cell migration assay The Journal of biological chemistry High 23184937
2018 USP9X interacts with and deubiquitinates FBW7, preventing its ubiquitin-dependent degradation. Usp9x deletion in mouse gut causes Fbw7 destabilization, reduces secretory cell differentiation, increases progenitor proliferation, and increases tumor burden in colitis-associated cancer. c-Myc heterozygosity rescues the proliferation and tumor phenotype, placing USP9X upstream of FBW7-c-Myc. Proteomics, co-immunoprecipitation, conditional mouse knockout, genetic epistasis (c-Myc heterozygosity), intestinal organoids The Journal of clinical investigation High 29346117
2019 USP9X interacts with, depolyubiquitylates, and stabilizes ALDH1A3 in mesenchymal glioblastoma stem cells (GSCs). Depletion of USP9X downregulates ALDH1A3, reducing self-renewal and tumorigenic capacity of MES GSCs; ectopic ALDH1A3 expression rescues these defects. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, rescue experiment, orthotopic xenograft model The Journal of clinical investigation High 30958800
2018 USP9X deubiquitinates and stabilizes YAP1 by removing polyubiquitin chains, preventing its proteasomal degradation. Depletion of USP9X increases YAP1 polyubiquitination and turnover, sensitizing breast cancer cells to chemotherapy. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, overexpression Oncogene Medium 29449692
2021 S-nitrosylation of USP9X (by nitric oxide) enables USP9X to deubiquitinate and stabilize MIB1, which activates NOTCH1 signaling. Genetic deletion of Usp9x in mice causes calcific aortic valve disease, and human calcified aortic valves show reduced S-nitrosylation of USP9X. Unbiased proteomics for S-nitrosylated proteins, co-immunoprecipitation, mouse genetic knockout, single-cell RNA-seq, in vitro deubiquitination assay Science advances High 33547080
2021 USP9X binds and deubiquitinates KDM4C, stabilizing it. Depletion of USP9X reduces KDM4C levels, impairing TGF-β2 transcription (KDM4C reduces H3K9me3 at the TGF-β2 promoter) and reducing radioresistance in lung cancer cells. Tandem affinity purification, co-immunoprecipitation, deubiquitination assay, RNAi knockdown, chromatin assays, in vitro and in vivo models Cell death and differentiation Medium 33558705
2017 USP9X physically associates with LATS kinase (and to lesser extent WW45, KIBRA, Angiomotin) and deubiquitinates/stabilizes LATS. Knockdown of USP9X downregulates LATS, promotes nuclear translocation of YAP/TAZ, and activates EMT. Deletion of Usp9x in mouse embryonic fibroblasts reduces LATS protein. Co-immunoprecipitation, gel filtration chromatography, RNAi knockdown, MEF knockout, YAP/TAZ reporter assay, soft agar assay Cancer research High 28720576
2017 USP9X (deubiquitylase USP9X) deubiquitinates and stabilizes LATS2, preventing its proteasomal degradation. USP9X ablation reduces LATS2 levels, activates YAP, and enhances oncogenic potential in pancreatic cancer cells. Identified by tandem affinity purification. Tandem affinity purification, co-immunoprecipitation, deubiquitination assay, RNAi knockdown, YAP reporter assay The Journal of biological chemistry Medium 29183995
2016 USP9X stabilizes XIAP by deubiquitylation in mitosis, conferring resistance to mitotic spindle poisons. USP9X knockdown reduces XIAP, sensitizes cells to spindle poisons, and delays lymphoma development in a murine Eμ-Myc model. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, murine lymphoma model, patient sample correlation EMBO molecular medicine Medium 27317434
2011 WP1130 directly inhibits USP9X deubiquitinase activity in CML cells, leading to downregulation of Mcl-1 and inducing apoptosis. Bcr-Abl undergoes K63-linked ubiquitin modification and aggresomal sequestration upon USP9X inhibition, blocking its signaling. Deubiquitinase activity assay, ubiquitin chain-type analysis, aggresome detection, apoptosis assays Blood Medium 21248063
2014 USP9X loss-of-function (Usp9x knockout mice) causes reduction in axonal growth and neuronal cell migration. Wild-type human USP9X rescues these defects, but three ID-associated missense/truncating variants fail to rescue axonal growth and show reduced localization in axonal growth cones. Usp9x knockout mouse, overexpression rescue with human USP9X variants, axon length measurement, neuronal migration assay, proteomics of Usp9x-null neurons American journal of human genetics High 24607389
2013 Conditional deletion of Usp9x from neural progenitors disrupts cellular organization of ventricular/subventricular zones and cortical plate, dramatically reduces axonal length (in vivo and in vitro), partly through failure of TGF-β signaling. Dorsal telencephalon-specific deletion results in corpus callosum reduction and hippocampal size decrease. Conditional Usp9x knockout (Nestin-cre and Emx1-cre), in vivo and in vitro axon length measurement, TGF-β signaling analysis PloS one High 23861879
2015 USP9X controls EGFR endocytosis and trafficking by deubiquitinating Eps15, an endocytic adaptor protein. USP9X depletion affects EGFR internalization; Eps15 monoubiquitination is essential for EGFR internalization. Systematic RNAi screen, co-immunoprecipitation, mapping of Eps15 ubiquitination sites, EGFR trafficking assays Current biology : CB High 26748853
2010 USP9X deubiquitinates EFA6 (exchange factor for Arf6) at newly forming epithelial cell contacts, transiently protecting it from proteasomal degradation and enabling tight junction biogenesis. Knockdown of either USP9X or EFA6 impairs tight junction formation; EFA6 overexpression rescues TJ biogenesis in USP9X-knockdown cells. Co-localization, co-immunoprecipitation, deubiquitination assay, RNAi knockdown, rescue experiment The EMBO journal High 20339350
2008 MARCH7 (E3 ubiquitin ligase) undergoes autoubiquitylation and associates with USP9X in the cytosol (and USP7 in the nucleus). USP9X stabilizes MARCH7 by deubiquitylation in a compartment-specific manner, and RNAi depletion of USP9X reduces MARCH7 levels. Co-immunoprecipitation, RNAi knockdown, overexpression, subcellular fractionation Traffic (Copenhagen, Denmark) Medium 18410486
2013 USP9X interacts with Bcl10 of the CBM (Carma1-Bcl10-Malt1) complex and removes TCR-induced ubiquitin chains from Bcl10, facilitating association of Carma1 with Bcl10-Malt1 and enabling NF-κB activation. Knockdown of USP9X attenuates T-cell proliferation and NF-κB activation upon TCR signaling. Co-immunoprecipitation, RNAi knockdown in human T-cell line and mouse primary T cells, adoptive transfer immunization Proceedings of the National Academy of Sciences of the United States of America High 23690623
2016 USP9X removes inhibitory monoubiquitination from ZAP70 in T lymphocytes upon TCR-dependent phosphorylation, which enhances USP9X catalytic activity. Absence of USP9X increases ZAP70 localization to early endosomes. In B lymphocytes, USP9X is required for BCR-dependent PKCβ kinase activity and CARMA1/Bcl-10/MALT-1 complex formation. Usp9X knockout mouse, co-immunoprecipitation, ubiquitination assay, endosome localization, kinase activity assay Journal of immunology (Baltimore, Md. : 1950) High 26936881
2016 USP9X deubiquitylates Angiomotin at lysine 496, stabilizing it and reducing YAP/TAZ activity as part of Hippo pathway regulation. Co-immunoprecipitation, deubiquitination assay, identification of specific ubiquitination site (K496), RNAi knockdown Cell discovery Medium 27462448
2017 USP9X is physically associated with centriolar satellite protein CEP131 and stabilizes it through its deubiquitinase activity. USP9X is an integral component of the centrosome required for centrosome biogenesis; loss-of-function impairs centrosome duplication. Co-immunoprecipitation, deubiquitinase activity assay, centrosome localization by microscopy, loss-of-function centrosome duplication assay Nature communications High 28361952
2017 USP9X is physically associated and spatially co-localized with centrosomal proteins PCM1 and CEP55, promoting their stabilization through its catalytic activity. USP9X centrosome localization depends on PCM1 and CEP55. Tandem mass tag labeling proteomics, co-immunoprecipitation, co-localization microscopy, deubiquitinase activity assay, RNAi knockdown The Journal of biological chemistry Medium 28620049
2019 USP9X interacts with and deubiquitinates ankyrin-G (ANK3); USP9X phosphorylation enhances their interaction and decreases ankyrin-G polyubiquitination, stabilizing ankyrin-G to maintain dendritic spine development. In forebrain-specific Usp9X knockout mice, ankyrin-G and multiple ANKRD-containing proteins are transiently reduced at 2 weeks; reduced cortical spine density persists into adulthood. Co-immunoprecipitation, ubiquitination assay, forebrain-specific conditional KO, dendritic spine density measurement, phosphorylation analysis Neuron High 31813652
2019 USP9X deubiquitylates DVL2 (Dishevelled 2) by removing ubiquitin to promote canonical WNT activation; increased DVL2 ubiquitylation (by WWP1 E3 ligase) is associated with DVL2 localization to actin-rich projections and activation of the WNT-PCP pathway. A WWP1-USP9X ubiquitin rheostat on DVL2 specifies pathway choice. Co-immunoprecipitation, deubiquitination assay, WNT reporter assays, PCP pathway assays, RNAi knockdown Cell reports High 31340145
2012 USP9X co-immunoprecipitates with mTOR along with Raptor and Rictor, components of mTORC1 and mTORC2. Knockdown of USP9X increases mTORC1 activity upon growth factor stimulation and increases mTORC2 activity upon differentiation initiation, accelerating C2C12 myoblast differentiation. Co-immunoprecipitation, RNAi knockdown, mTOR kinase activity assay, myoblast differentiation assay The Journal of biological chemistry Medium 22544753
2017 USP9X deubiquitylating activity stabilizes RAPTOR protein (mTORC1 scaffold). RAPTOR physically associates with USP9X in embryonic brains; RAPTOR protein level is directly proportional to USP9X in both gain- and loss-of-function experiments; USP9X deubiquitylating activity opposes proteasomal degradation of RAPTOR. Loss of Usp9x causes reduced mTORC1 signaling and neural progenitor arrest in G0. Co-immunoprecipitation from embryonic brain, gain/loss-of-function in cultured cells and neurospheres, mTORC1 signaling assay, EdU proliferation assay Scientific reports Medium 28341829
2016 USP9X interacts with and deubiquitinates CLASPIN in an S-phase-specific manner, stabilizing it during DNA replication. USP9X depletion impairs DNA replication fork progression (similar to CLASPIN depletion), causes excessive endogenous DNA damage, and compromises CHK1 activation in response to replication stress. Restoration of CLASPIN in USP9X-depleted cells partially suppresses DNA damage accumulation. Quantitative proteomics, co-immunoprecipitation, RNAi knockdown, DNA fiber assay, CHK1 activation assay, rescue experiment Cancer research High 26921344
2015 USP9X interacts with PRICKLE proteins through their carboxy-termini and deubiquitinates PRICKLE, protecting it from proteasomal degradation. USP9X deficiency in mouse forebrain neurons reduces Prickle2 protein. Genetic reduction of fat facets (USP9X Drosophila orthologue) or treatment with WP1130 suppresses prickle-mediated seizures, placing USP9X in the Prickle seizure-suppression pathway. Interactome definition, co-immunoprecipitation, deubiquitination assay, forebrain Usp9x conditional KO (Prickle2 levels), Drosophila genetic epistasis, pharmacological WP1130 treatment PLoS genetics High 25763846
2017 Ets-1 transcription factor is deubiquitinated and stabilized by Usp9x, preventing its proteasomal destruction. Usp9x knockdown or inhibition reduces Ets-1 levels, decreasing NRAS expression and suppressing melanoma tumorigenicity. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, in vitro and in vivo tumor assays Nature communications Medium 28198367
2016 USP9X interacts with TRB3 (pseudokinase) serving as scaffold for USP9X. USP9X deubiquitinates and stabilizes TRB3, and also deubiquitinates and activates Mind Bomb 1 (E3 ligase for JAG1 ubiquitination-mediated endocytosis), thereby activating Notch signaling in the signal-sending cell under cellular stress. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, Notch reporter assay Oncogene Medium 27593927
2016 USP9X binds and deubiquitinates β-catenin, removing Lys48-linked polyubiquitin chains to prevent proteasomal degradation, thereby activating Wnt/β-catenin signaling and promoting glioma cell proliferation. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, cell cycle analysis, in vivo xenograft Oncotarget Medium 27783990
2019 USP9X interacts with BCL9 and removes Lys63-linked polyubiquitin from Lys-212 of BCL9. This deubiquitination facilitates formation of the β-catenin-BCL9-PYGO complex, potentiating transcriptional activation of Wnt/β-catenin target genes. nano-HPLC-MS/MS, co-immunoprecipitation, deubiquitination assay, ubiquitination site mapping, chromatin immunoprecipitation, Wnt reporter assay The Journal of biological chemistry Medium 31073027
2019 USP9X stabilizes PBX1 by attenuating its Lys48-linked polyubiquitination. Co-immunoprecipitation confirmed USP9X-PBX1 interaction. USP9X inhibition induces PBX1 degradation and promotes prostate cancer cell apoptosis. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, pharmacological inhibition, apoptosis assay The Journal of biological chemistry Medium 30718275
2017 USP9X deubiquitinates and stabilizes TTK (dual specificity protein kinase) via removal of K48-linked ubiquitin chains, through direct interaction. USP9X knockdown reduces TTK protein levels and inhibits NSCLC cell proliferation, migration and tumorigenesis. Chemical labeling quantitative proteomics, co-immunoprecipitation, deubiquitination assay, ubiquitin chain-type analysis, in vitro and in vivo tumor assays Theranostics Medium 29721084
2020 USP9X removes Lys63-linked ubiquitin from RICTOR (mTORC2 scaffold), promoting RICTOR interaction with mTOR and facilitating mTORC2 assembly and activity. This process is stimulated by growth factors. Co-immunoprecipitation, deubiquitination assay, ubiquitin chain-type analysis, mTORC2 kinase activity assay, human cell lines and mice Cell reports High 33378666
2020 CDC14B phosphatase antagonizes CDK1-mediated phosphorylation of USP9X at serine 2563. Serine 2563 phosphorylation of USP9X is essential for its mitotic activity: phospho-USP9X deubiquitylates and stabilizes WT1 (Wilms' tumor protein) during mitosis, and WT1 acts as a mitotic transcription factor driving CXCL8/IL-8 expression to promote mitotic survival. Unbiased proteome-wide phosphorylation screening, in vitro phosphorylation assay, co-immunoprecipitation, deubiquitination assay, reporter gene assay Nature communications High 32152317
2021 USP9X interacts with and stabilizes Makorin 2 and ZNF598 (ubiquitin E3 ligases of the ribosomal quality control pathway). Chemical inhibition or depletion of USP9X reduces levels of Makorins and ZNF598, impairing the ribosomal quality control/stalling pathway. Small-molecule USP9X inhibitor, proteomics analysis, co-immunoprecipitation, ribosomal stalling assays The Journal of cell biology High 33507233
2019 USP9X interacts with and deubiquitinates eIF4A1 at Lys-369, preventing its ubiquitin-mediated degradation. USP9X dysfunction increases eIF4A1 ubiquitination and degradation, impairing cap-dependent translation initiation and reducing protein synthesis of pro-oncogenic mRNAs such as c-Myc and XIAP. Tandem affinity purification, co-immunoprecipitation, ubiquitination site mapping, nascent protein synthesis assay, cap-dependent translation assay Nucleic acids research High 29228324
2018 USP9X interacts with and deubiquitinates BMAL1 (core circadian clock protein), reducing its ubiquitination, enhancing its stability and protein level, and increasing its transcriptional activity. USP9X knockdown decreases the amplitude of cellular circadian rhythm without affecting period or phase. Affinity purification, mass spectrometry, co-immunoprecipitation, deubiquitination assay, bioluminescence circadian rhythm measurement The Biochemical journal Medium 29626158
2017 USP9X is methylated at arginine residues, enabling its interaction with the Tudor domain of TDRD3. This interaction is mediated through the Tudor domain of TDRD3 and arginine methylation of USP9X. USP9X depletion increases TDRD3 ubiquitination; TDRD3 is essential for USP9X stress granule localization. GST pulldown, co-immunoprecipitation, arginine methylation identification, RNAi knockdown, stress granule localization by microscopy, Tdrd3-null MEFs Cell discovery Medium 28101374
2017 TGF-β activates ERK which phosphorylates SMAD4 at Thr277, facilitating SMAD4-USP9X interaction. USP9X inhibits TIF1γ from binding and monoubiquitinating SMAD4, thereby maintaining SMAD4 nuclear retention and TGF-β/SMAD3-mediated transcription of Twist and Snail, promoting breast cancer metastasis. Co-immunoprecipitation, phospho-SMAD4 mutant analysis, chromatin retention assay, luciferase reporter, RNAi knockdown Cancer research Medium 28115363
2005 USP9X (DFFRX) interacts with Doublecortin (DCX) through a novel recognition domain outside USP9X's catalytic site. No ubiquitinated forms of DCX were detected, suggesting this interaction is non-catalytic. USP9X associates with microtubules at specific subcellular compartments enriched in DCX. Targeted mutagenesis, co-localization, co-immunoprecipitation, ubiquitination detection (negative result for DCX) Molecular and cellular neurosciences Medium 15607950
2017 NPHP5 (nephrocystin-5) directly binds USP9X. In G0/G1/S phase, a pool of cytoplasmic USP9X is recruited to the centrosome by NPHP5, protecting NPHP5 from ubiquitination and favouring cilia assembly. In G2/M, USP9X dissociates from the centrosome, allowing BBS11 to K63-ubiquitinate NPHP5, triggering delocalization and cilia loss. Co-immunoprecipitation, ubiquitination assay (K48/K63 typing), cell cycle synchronization, cilia assembly assay, RNAi knockdown PLoS genetics High 28498859
2019 USP9X binds PCM1 and antagonizes MIB1-mediated PCM1 ubiquitylation, protecting PCM1 from proteasomal degradation. Knockdown of USP9X reduces PCM1 protein levels and disrupts centriolar satellite integrity, causing satellite proteins such as CEP290 to relocalize to centrosomes. Co-immunoprecipitation, deubiquitylation assay, RNAi knockdown, centriolar satellite microscopy, epistasis (MIB1 knockdown rescues PCM1 levels) Journal of cell science High 30584065
2019 SNX17 recruits USP9X to antagonize MIB1-induced ubiquitination and degradation of PCM1 during serum-starvation-induced ciliogenesis. SNX17 deficiency leads to enhanced degradation of both USP9X and PCM1 and disrupts ciliogenesis. Co-immunoprecipitation, ubiquitination assay, ciliogenesis assay, SNX17 knockdown, RNAi Cells Medium 31671755
2019 USP9X deubiquitinates and stabilizes PTGES (prostaglandin E synthase) by physically interacting with it and preventing proteasome-directed degradation, thereby promoting PGE2 synthesis and metastatic features of NSCLC. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, in vivo metastasis model American journal of cancer research Medium 31285948
2018 USP9X deubiquitinates and stabilizes BRCA1. Reciprocal co-IP confirms USP9X-BRCA1 interaction. Depletion of USP9X reduces BRCA1 abundance, shortens its half-life, increases its ubiquitination, reduces HR efficiency, and sensitizes cells to PARP inhibitors and MMS. Catalytically dead USP9X (C1566S) does not upregulate BRCA1. Reciprocal co-immunoprecipitation, RNAi knockdown, overexpression of WT vs. C1566S mutant, HR assay, drug sensitivity assay Cancer medicine Medium 31512408
2022 USP9X removes K63-linked polyubiquitin from SR-A1 (class A1 scavenger receptor) at the K27 site, reducing SR-A1 cell surface internalization after ox-LDL binding. K27R mutation of SR-A1 attenuates USP9X knockdown-induced ox-LDL uptake, establishing USP9X as a regulator of SR-A1 ubiquitination and macrophage foam cell formation. Loss-of-function screening, co-immunoprecipitation, site-specific mutagenesis (K27R), ubiquitin chain type analysis, macrophage foam cell assay, macrophage-specific KO mouse The Journal of clinical investigation High 35389885
2022 USP9X deubiquitinates and stabilizes Snail1, promoting its function in epithelial-mesenchymal transition in TNBC. Depletion of USP9X downregulates Snail1, inhibits migration/invasion, and increases sensitivity to cisplatin and paclitaxel; reconstitution of Snail1 in USP9X-depleted cells partially reverses these effects. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, Snail1 rescue experiment, in vitro and in vivo metastasis assays Journal of cellular physiology Medium 35506169
2021 USP9X deubiquitinates NLRP3, preventing its ubiquitination and stabilizing NLRP3 protein (not mRNA). USP9X knockdown increases NLRP3 ubiquitination and reduces NLRP3 inflammasome activation and pyroptosis in alveolar epithelial cells; NLRP3 overexpression rescues these effects. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, overexpression rescue, pyroptosis assay Cell biology international Medium 36525374
2023 USP9X deubiquitinates and stabilizes NRP1 (neuropilin-1), with USP9X-mediated NRP1 deubiquitination enhancing hepatic stellate cell (HSC) activation and liver fibrosis. Identified by co-immunoprecipitation and GST pulldown with in vivo and in vitro ubiquitination assays. Co-immunoprecipitation, GST pulldown, in vivo and in vitro ubiquitination assay, immunohistochemistry, RNAi knockdown Cell death & disease Medium 36653359
2018 USP9X deubiquitinates Cx43 (connexin 43) by directly binding to Cx43's C-terminal Tyr286, preventing its degradation. USP9X overexpression suppresses high glucose-induced EMT in NRK-52E cells in a deubiquitinase activity-dependent manner (catalytically inactive C1556S mutant has no effect). CRISPR/Cas9 SAM overexpression, RNAi knockdown, co-immunoprecipitation, ubiquitination assay, catalytic mutant (C1556S), EMT marker quantification Biochemical pharmacology Medium 33857489
2018 USP9X deubiquitinates Nrf2, reducing its ubiquitination level and promoting Nrf2-ARE pathway activation, thereby limiting ROS production and extracellular matrix accumulation in diabetic renal fibrosis conditions. Catalytically inactive USP9X-C1556S fails to stabilize Nrf2. Co-immunoprecipitation, ubiquitination assay, catalytic mutant (C1556S), Nrf2-ARE reporter assay, ROS measurement, RNAi knockdown Experimental cell research Medium 32442538
2018 USP9X stabilizes ZBTB38 (methyl-CpG-binding protein) by interacting with it and deubiquitinating it. USP9X itself is stabilized by oxidative stress. Both USP9X and ZBTB38 are required to limit basal ROS generation and toxicity of acute oxidative stress. Co-immunoprecipitation, deubiquitination assay, RNAi knockdown, ROS measurement, protein stability assay Nucleic acids research Medium 29490077
2017 USP9X is required for spermatogenesis: germ cell-specific conditional deletion of Usp9x results in apoptotic cell death at the early spermatocyte stage and subsequent aberrant spermiogenesis, establishing a critical role for USP9X in the mitosis-to-meiosis transition in male germ cells. Vasa-Cre conditional Usp9x knockout mouse, histology, apoptosis detection Reproduction (Cambridge, England) Medium 28559472

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature 535 20023629
2012 The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature 279 22699621
2008 Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. The Biochemical journal 187 18254724
2015 La FAM fatale: USP9X in development and disease. Cellular and molecular life sciences : CMLS 166 25672900
2010 Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. The Journal of biological chemistry 156 21173155
2011 α-Synuclein fate is determined by USP9X-regulated monoubiquitination. Proceedings of the National Academy of Sciences of the United States of America 153 22065755
2009 Ubiquitin-like sequence in ASK1 plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death. Molecular cell 124 20005844
2014 Mutations in USP9X are associated with X-linked intellectual disability and disrupt neuronal cell migration and growth. American journal of human genetics 121 24607389
2022 Disruption of USP9X in macrophages promotes foam cell formation and atherosclerosis. The Journal of clinical investigation 116 35389885
2017 USP9X regulates centrosome duplication and promotes breast carcinogenesis. Nature communications 108 28361952
2011 Bcr-Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis. Blood 106 21248063
2006 The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. The Journal of biological chemistry 103 17038327
2012 Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. The Journal of biological chemistry 102 23184937
2018 The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer. The Journal of clinical investigation 98 29346117
2019 USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells. The Journal of clinical investigation 81 30958800
2021 Nitric oxide prevents aortic valve calcification by S-nitrosylation of USP9X to activate NOTCH signaling. Science advances 78 33547080
2018 The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance through YAP1 stabilization. Oncogene 78 29449692
2021 USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription. Cell death and differentiation 76 33558705
2014 MicroRNA-26b inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting USP9X. BMC cancer 76 24890815
2017 Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway. Cancer research 75 28720576
2012 The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC cancer 75 23171055
2008 The ubiquitin E3 ligase MARCH7 is differentially regulated by the deubiquitylating enzymes USP7 and USP9X. Traffic (Copenhagen, Denmark) 74 18410486
2015 USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15. Current biology : CB 71 26748853
2013 Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis. PloS one 70 23861879
2015 WP1130 increases doxorubicin sensitivity in hepatocellular carcinoma cells through usp9x-dependent p53 degradation. Cancer letters 65 25749422
2014 Usp9x- and Noxa-mediated Mcl-1 downregulation contributes to pemetrexed-induced apoptosis in human non-small-cell lung cancer cells. Cell death & disease 65 24991768
2018 A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer. Theranostics 64 29721084
2018 USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy. Cancer letters 62 30118840
2018 Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells. Biochemical and biophysical research communications 60 29605299
2015 Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS genetics 60 25763846
2016 USP9X stabilizes XIAP to regulate mitotic cell death and chemoresistance in aggressive B-cell lymphoma. EMBO molecular medicine 59 27317434
2012 Deubiquitinase USP9x confers radioresistance through stabilization of Mcl-1. Neoplasia (New York, N.Y.) 58 23097624
2019 Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling. Biological psychiatry 57 31443933
2017 Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma. Nature communications 57 28198367
2014 Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X. The Journal of experimental medicine 56 25200027
2016 Cellular stress induces TRB3/USP9x-dependent Notch activation in cancer. Oncogene 55 27593927
2016 Deubiquitinase USP9X deubiquitinates β-catenin and promotes high grade glioma cell growth. Oncotarget 54 27783990
2013 Regulation of T cell function by the ubiquitin-specific protease USP9X via modulating the Carma1-Bcl10-Malt1 complex. Proceedings of the National Academy of Sciences of the United States of America 54 23690623
2021 Therapeutic inhibition of USP9x-mediated Notch signaling in triple-negative breast cancer. Proceedings of the National Academy of Sciences of the United States of America 53 34518219
2017 Deubiquitylase USP9X suppresses tumorigenesis by stabilizing large tumor suppressor kinase 2 (LATS2) in the Hippo pathway. The Journal of biological chemistry 52 29183995
2011 Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1. Molecular cancer therapeutics 52 21566062
2010 USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly. The EMBO journal 51 20339350
2009 USP9X enhances the polarity and self-renewal of embryonic stem cell-derived neural progenitors. Molecular biology of the cell 51 19176755
2012 Ubiquitin-specific peptidase 9, X-linked (USP9X) modulates activity of mammalian target of rapamycin (mTOR). The Journal of biological chemistry 48 22544753
2019 Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development. Neuron 47 31813652
2019 Inhibition of the deubiquitinase USP9x induces pre-B cell homeobox 1 (PBX1) degradation and thereby stimulates prostate cancer cell apoptosis. The Journal of biological chemistry 46 30718275
2019 USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification. Cell reports 46 31340145
2015 Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo. Oncotarget 45 26008975
2016 The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase. Cancer research 44 26921344
2005 Sexually dimorphic expression of Usp9x is related to sex chromosome complement in adult mouse brain. The European journal of neuroscience 43 15978012
2017 Aberrant Phosphorylation of SMAD4 Thr277-Mediated USP9x-SMAD4 Interaction by Free Fatty Acids Promotes Breast Cancer Metastasis. Cancer research 42 28115363
2019 WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP. Cancers 41 30862047
2016 Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKCβ Kinase Activity. Journal of immunology (Baltimore, Md. : 1950) 39 26936881
2017 USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors. Scientific reports 38 28341829
2014 USP9X downregulation renders breast cancer cells resistant to tamoxifen. Cancer research 38 25028367
2021 The deubiquitylase USP9X controls ribosomal stalling. The Journal of cell biology 37 33507233
2019 Inhibition of USP9X induces apoptosis in FLT3-ITD-positive AML cells cooperatively by inhibiting the mutant kinase through aggresomal translocation and inducing oxidative stress. Cancer letters 35 30946869
2019 Targeting USP9x/SOX2 axis contributes to the anti-osteosarcoma effect of neogambogic acid. Cancer letters 35 31605775
2017 USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to regulate ciliogenesis. PLoS genetics 35 28498859
2016 Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms. Cell death & disease 35 26775694
2016 Deubiquitylating enzyme USP9x regulates hippo pathway activity by controlling angiomotin protein turnover. Cell discovery 35 27462448
2005 Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes. Molecular and cellular neurosciences 34 15607950
2017 Usp9x Promotes Survival in Human Pancreatic Cancer and Its Inhibition Suppresses Pancreatic Ductal Adenocarcinoma In Vivo Tumor Growth. Neoplasia (New York, N.Y.) 32 29248719
2015 USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer cells expressing mid-to-high MCL1. Cancer biology & therapy 32 25692226
2023 USP9X-mediated NRP1 deubiquitination promotes liver fibrosis by activating hepatic stellate cells. Cell death & disease 31 36653359
2019 USP9X stabilizes BRCA1 and confers resistance to DNA-damaging agents in human cancer cells. Cancer medicine 31 31512408
2017 Arginine methylation of USP9X promotes its interaction with TDRD3 and its anti-apoptotic activities in breast cancer cells. Cell discovery 31 28101374
2017 WP1130 increases cisplatin sensitivity through inhibition of usp9x in estrogen receptor-negative breast cancer cells. American journal of translational research 31 28469783
2022 Targeting USP9X-AMPK Axis in ARID1A-Deficient Hepatocellular Carcinoma. Cellular and molecular gastroenterology and hepatology 30 35390516
2022 Deubiquitinating enzyme USP9X regulates metastasis and chemoresistance in triple-negative breast cancer by stabilizing Snail1. Journal of cellular physiology 30 35506169
2019 RNA sequencing identifies a novel USP9X-USP6 promoter swap gene fusion in a primary aneurysmal bone cyst. Genes, chromosomes & cancer 30 30767316
2019 Stabilization of PTGES by deubiquitinase USP9X promotes metastatic features of lung cancer via PGE2 signaling. American journal of cancer research 30 31285948
2016 Usp9x-deficiency disrupts the morphological development of the postnatal hippocampal dentate gyrus. Scientific reports 30 27181636
2014 Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma. Cancer biology & therapy 30 24841553
2021 USP9X deubiquitinates connexin43 to prevent high glucose-induced epithelial-to-mesenchymal transition in NRK-52E cells. Biochemical pharmacology 29 33857489
2005 Spatially and temporally specific expression in mouse hippocampus of Usp9x, a ubiquitin-specific protease involved in synaptic development. Journal of neuroscience research 29 15723417
2020 Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival. Nature communications 28 32152317
2020 Missense variant contribution to USP9X-female syndrome. NPJ genomic medicine 28 33298948
2017 The X-linked deubiquitinase USP9X is an integral component of centrosome. The Journal of biological chemistry 28 28620049
2017 Loss of Usp9x disrupts cell adhesion, and components of the Wnt and Notch signaling pathways in neural progenitors. Scientific reports 28 28808228
2016 USP9X destabilizes pVHL and promotes cell proliferation. Oncotarget 27 27517496
2020 mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RICTOR. Cell reports 26 33378666
2017 Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice. Reproduction (Cambridge, England) 25 28559472
2017 Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer. Oncology reports 25 29130109
2024 Cellular functions, molecular signalings and therapeutic applications: Translational potential of deubiquitylating enzyme USP9X as a drug target in cancer treatment. Biochimica et biophysica acta. Reviews on cancer 24 38582329
2019 Deubiquitylase USP9X maintains centriolar satellite integrity by stabilizing pericentriolar material 1 protein. Journal of cell science 24 30584065
2019 USP9X-mediated deubiquitination of B-cell CLL/lymphoma 9 potentiates Wnt signaling and promotes breast carcinogenesis. The Journal of biological chemistry 24 31073027
2021 Elevated USP9X drives early-to-late-stage oral tumorigenesis via stabilisation of anti-apoptotic MCL-1 protein and impacts outcome in oral cancers. British journal of cancer 23 34079080
2018 Stabilization of the methyl-CpG binding protein ZBTB38 by the deubiquitinase USP9X limits the occurrence and toxicity of oxidative stress in human cells. Nucleic acids research 23 29490077
2018 Deubiquitinating enzyme USP9X regulates cellular clock function by modulating the ubiquitination and degradation of a core circadian protein BMAL1. The Biochemical journal 23 29626158
2023 Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis. Clinical and experimental hypertension (New York, N.Y. : 1993) 22 36890708
2022 USP9X promotes lipopolysaccharide-stimulated acute lung injury by deubiquitination of NLRP3. Cell biology international 22 36525374
2020 USP9X prevents AGEs-induced upregulation of FN and TGF-β1 through activating Nrf2-ARE pathway in rat glomerular mesangial cells. Experimental cell research 21 32442538
2019 SNX17 Recruits USP9X to Antagonize MIB1-Mediated Ubiquitination and Degradation of PCM1 during Serum-Starvation-Induced Ciliogenesis. Cells 21 31671755
2018 USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1. Nucleic acids research 21 29228324
2015 β-catenin is regulated by USP9x and mediates resistance to TRAIL-induced apoptosis in breast cancer. Oncology reports 21 26717875
2019 USP9X promotes LPS-induced pulmonary epithelial barrier breakdown and hyperpermeability by activating an NF-κBp65 feedback loop. American journal of physiology. Cell physiology 20 31216195
2016 Deubiquitylating enzyme, USP9X, regulates proliferation of cells of head and neck cancer lines. Cell proliferation 20 27374971
2002 Stage- and sex-dependent expressions of Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice. Mechanisms of development 20 14516667
2023 Roles of USP9X in cellular functions and tumorigenesis (Review). Oncology letters 19 37920433

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