Affinage

UXT

Protein UXT · UniProt Q9UBK9

Length
157 aa
Mass
18.2 kDa
Annotated
2026-06-11
38 papers in source corpus 30 papers cited in narrative 30 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

UXT (ART-27) is a small prefoldin-like protein that functions as a context-dependent transcriptional cofactor and chaperone-adaptor, partitioning between the nucleus and cytoplasm in two isoforms (nuclear V2, cytoplasmic V1) to regulate hormone signaling, innate immunity, and selective autophagy (PMID:11854421, PMID:17620405, PMID:21307340). In the nucleus it was first defined as an androgen receptor coactivator binding the AR N-terminal AF-1a region and enhancing AR-driven transcription while suppressing androgen-mediated proliferation (PMID:11854421, PMID:14711828), and it more broadly modulates transcription factor activity by interacting with NF-κB as an essential, recruitable enhanceosome component (PMID:17620405), with Foxp3 to stabilize regulatory T cell suppressive function (PMID:24136450), and with the Notch intracellular domain to block NICD–RBP-Jκ activation (PMID:25617435). Its activity as an NF-κB cofactor is tuned by post-translational control: EBV BGLF4 kinase phosphorylates UXT at Thr3 to disrupt the UXT–NF-κB interaction and maintain viral latency (PMID:22933289), and SCF(Fbxo7) ubiquitinates UXT-V2 to drive its proteasomal turnover (PMID:33010352). In the cytoplasm, UXT-V1 enters TNF receptor signaling by binding TRAF2 to prevent FADD recruitment and apoptotic complex II formation (PMID:21307340), and bridges TRAF3 to MAVS on mitochondria to enable antiviral IFN-β induction (PMID:22131337). UXT also acts as a selective autophagy adaptor, forming β-hairpin-mediated higher-order oligomers that cluster ubiquitinated aggregates with p62/SQSTM1 for aggrephagy (PMID:33782410, PMID:40092611) and directing SQSTM1-dependent autophagic degradation of STING1 to dampen cGAS-STING innate signaling (PMID:35543189). In vivo, conditional Uxt deletion is embryonic lethal and demonstrates essential roles in spermatogenesis and blood-testis-barrier integrity (PMID:29649254, PMID:32678429) and in photoreceptor survival via MTOR-dependent restraint of autophagy (PMID:32744119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Established UXT as a nuclear androgen receptor coactivator, defining its founding identity as a transcriptional cofactor rather than an orphan protein.

    Evidence Y2H, nuclear-extract Co-IP, transcriptional reporter assays and velocity gradient sedimentation in LNCaP/HeLa cells

    PMID:11854421

    Open questions at the time
    • Identity of the multiprotein complex members unresolved
    • Mechanism by which UXT enhances AR transactivation not defined
  2. 2004 Medium

    Showed UXT functionally rewires AR output, suppressing proliferation while enhancing differentiation gene transcription, implying a growth-suppressive coactivator role.

    Evidence Inducible overexpression in LNCaP cells with proliferation and PSA transcription readouts

    PMID:14711828

    Open questions at the time
    • Single cell line
    • Endogenous-level confirmation lacking
  3. 2005 Medium

    Connected disease-associated AR mutations to altered UXT physical binding, linking the AR–UXT interface to androgen-pathology phenotypes; concurrently placed UXT at centrosomes as essential for viability.

    Evidence AR point-mutant Co-IP and reporter assays; immunofluorescence, gamma-tubulin Co-IP and siRNA in mammalian cells

    PMID:15919721 PMID:16221885

    Open questions at the time
    • Whether centrosomal and nuclear pools are the same functional protein unclear
    • Cause of knockdown lethality not mechanistically defined
  4. 2007 High

    Defined the nuclear V2 isoform as a recruitable NF-κB enhanceosome component required for NF-κB transcription and survival, and extended cofactor reach to the EVI1 repressor.

    Evidence Y2H, Co-IP, RNAi with gene-expression and apoptosis readouts; transformation assays with Evi1 deletion mutants

    PMID:17620405 PMID:17635584

    Open questions at the time
    • Molecular basis of enhanceosome recruitment unresolved
    • How UXT discriminates among transcription factors unknown
  5. 2011 High

    Resolved isoform-specific cytoplasmic functions, showing UXT-V1 binds TRAF2 to block apoptotic complex II and binds TRAF3 to assemble the MAVS antiviral signalosome on mitochondria.

    Evidence Subcellular fractionation, Co-IP, domain mapping, siRNA knockdown and reporter assays

    PMID:21307340 PMID:22131337

    Open questions at the time
    • Structural detail of TRAF-binding motif engagement limited
    • Coordination between V1 and V2 functions unaddressed
  6. 2012 High

    Identified a phosphoswitch (BGLF4 at Thr3) controlling the UXT–NF-κB interaction, establishing post-translational regulation of UXT cofactor activity and its requirement for EBV latency.

    Evidence In vitro kinase assay, Thr3 mutagenesis with functional validation, shRNA knockdown in EBV-positive cells

    PMID:22933289

    Open questions at the time
    • Host kinases acting on Thr3 not identified
    • Structural consequence of phosphorylation unmapped
  7. 2013 Medium

    Expanded the cofactor repertoire and assigned in vivo pathway roles: UXT stabilizes Foxp3 in Tregs, recruits VHL to modulate AR ubiquitination, and represses Notch signaling to control angiogenesis.

    Evidence Co-IP with domain mapping, ChIP, ubiquitination assays, zebrafish knockdown with Notch-blockade rescue, SARM caspase assays

    PMID:23961993 PMID:24021647 PMID:24136450 PMID:25617435

    Open questions at the time
    • Whether these interactions are direct or complex-mediated varies by study
    • Tissue-specific selectivity among partners unexplained
  8. 2015 Medium

    Implicated UXT as a tumor-context oncogene through MDMX binding and p53 suppression, contrasting with its growth-suppressive AR-cofactor role.

    Evidence Co-IP, pathway reporter screen, knockdown/overexpression and xenograft in sarcoma cells

    PMID:25974965

    Open questions at the time
    • Reconciliation with growth-suppressive AR role not addressed
    • Directness of UXT–MDMX effect on p53 unclear
  9. 2016 Medium

    Placed UXT within a chromatin cofactor module with EZH1/SUZ12 that controls p65 and Pol II recruitment to NF-κB targets independent of H3K27 methylation.

    Evidence Co-IP, siRNA knockdown, ChIP-seq and reporter assays

    PMID:27127229

    Open questions at the time
    • Stoichiometry and architecture of the UXT–EZH1–SUZ12 complex undefined
    • Whether complex assembles before or after NF-κB activation unknown
  10. 2017 Medium

    Demonstrated cytoplasmic relocalization and proteasomal turnover as a regulatory mode releasing UXT-mediated repression of ER, broadening UXT's nuclear receptor regulation beyond AR.

    Evidence Y2H, Co-IP, proteasome inhibitor rescue, fractionation and ER reporter assays

    PMID:28106301

    Open questions at the time
    • E3 ligase mediating LOX-PP-driven degradation not identified
    • Physiological context of ER repression unclear
  11. 2018 High

    Provided the first in vivo essentiality evidence: Uxt is embryonic lethal and required cell-autonomously in the germline for spermatogonial transcription programs.

    Evidence Constitutive and germline-conditional knockout mice with histology and RNA-seq

    PMID:29649254

    Open questions at the time
    • Direct transcriptional targets driving the spermatogenesis phenotype not pinpointed
    • Which UXT partner mediates the germline role unknown
  12. 2019 Medium

    Linked UXT loss to prostate neoplasia and genome instability via derepression of retroelements, connecting UXT to suppression of transposon activity.

    Evidence Prostate-specific conditional knockout mice, retrotransposition assays and DNA-damage markers

    PMID:30774773

    Open questions at the time
    • Mechanism by which UXT restrains LINE-1/Alu undefined
    • Relationship to its transcriptional cofactor activity unresolved
  13. 2020 High

    Defined tissue-level physiological roles: Sertoli-cell UXT maintains blood-testis-barrier integrity, and retinal UXT preserves photoreceptors by restraining autophagy through MTOR.

    Evidence Sertoli- and retina-conditional knockout mice with EM, tracer permeability, ERG, TUNEL and autophagic-flux assays

    PMID:32678429 PMID:32744119

    Open questions at the time
    • How UXT regulates MTOR activity mechanistically not resolved
    • Whether autophagy regulation is direct or transcriptional unclear
  14. 2020 High

    Identified SCF(Fbxo7) as the E3 ligase driving UXT-V2 ubiquitination and turnover, establishing degradative control that tunes UXT's NF-κB cofactor pool.

    Evidence In vitro and in vivo ubiquitination assays, chain-linkage analysis, CHX chase, domain mapping and reporter assays

    PMID:33010352

    Open questions at the time
    • Signals triggering Fbxo7-mediated degradation not defined
    • Functional meaning of mixed K48/K63 chains unresolved
  15. 2021 High

    Recast UXT as a selective-autophagy adaptor that oligomerizes to bridge ubiquitinated aggregates to p62/SQSTM1, with protective effect in a motor-neuron degeneration model.

    Evidence Y2H, Co-IP, in vitro aggregate-binding, Xenopus SOD1(A4V) model with interaction-disrupting mutants

    PMID:33782410

    Open questions at the time
    • Selectivity of aggregate recognition undefined
    • Relationship to its prefoldin-like chaperone identity not established
  16. 2022 High

    Showed UXT directs SQSTM1-dependent autophagic degradation of STING1, providing a brake on cGAS-STING innate immunity validated in viral-infection and lupus mouse models.

    Evidence Co-IP, autophagy inhibitors, conditional knockout mouse models and PBMC functional assays

    PMID:35543189

    Open questions at the time
    • How UXT selects STING1 as cargo undefined
    • Interplay with UXT's NF-κB and antiviral roles not integrated
  17. 2025 Medium

    Provided structural mechanism for the autophagy-adaptor function, showing β-hairpin-mediated hexameric and higher-order oligomerization is required for aggregate clearance, and a new antiviral mode in which UXT-V2 recruits TRIM21 for K48-ubiquitination of HSV-2 glycoprotein B.

    Evidence Structural homology modeling with oligomerization mutants and in vitro/Xenopus clearance assays; Co-IP, K48 ubiquitination assays and viral replication assays

    PMID:40092611 PMID:40907749

    Open questions at the time
    • Experimental structure of the oligomer not determined
    • Whether oligomerization governs non-autophagy functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small protein coordinates its many partner-specific roles — isoform partitioning, oligomeric state, and post-translational switching — into a unified molecular logic remains unresolved.
  • No experimental atomic structure of UXT in any complex
  • Rules governing selection among AR, NF-κB, Notch, Foxp3, p62 and STING1 partners unknown
  • Mechanistic link between prefoldin-like chaperone identity and transcriptional cofactor function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3 R-HSA-392499 Metabolism of proteins 2
Partners
ARFBXO7FOXP3SQSTM1STING1TRAF2TRAF3TRIM21
Complex memberships
MAVS–TRAF3 mitochondrial signalosomeNF-κB enhanceosomeTNF receptor signaling complexURI/UXT prefoldin-like complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ART-27 (UXT) was identified as a coactivator that interacts predominantly with the AR N-terminal region containing AF-1a (AR residues 153-336), localizes to the nucleus, and increases AR transcriptional activity when overexpressed. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Native ART-27 is part of a multiprotein complex as shown by velocity gradient sedimentation of HeLa nuclear extracts. Yeast two-hybrid, co-immunoprecipitation from nuclear extracts, overexpression in mammalian cells, LexA fusion transcriptional assays, velocity gradient sedimentation Molecular biology of the cell High 11854421
2004 ART-27 (UXT) expression in LNCaP prostate cancer cells inhibits androgen-mediated cellular proliferation while enhancing androgen-mediated transcription of the PSA gene, establishing a growth-suppressive and differentiation-promoting function for ART-27 as an AR cofactor. Regulated expression (inducible overexpression) in LNCaP cells with proliferation and PSA transcription readouts The Journal of biological chemistry Medium 14711828
2005 Naturally occurring AR mutations from prostate cancer (AR P340L) and androgen insensitivity syndrome (AR E2K) show reduced transcriptional responses to ART-27 coactivation. AR E2K shows reduced ART-27 protein association by co-immunoprecipitation, while AR P340L shows increased ART-27 association despite reduced transcriptional activation, indicating that aberrant AR–ART-27 physical interaction interferes with normal coactivator function. Transcriptional reporter assays, co-immunoprecipitation, AR mutation analysis Molecular endocrinology Medium 15919721
2005 UXT localizes to centrosomes and is associated with gamma-tubulin. Overexpression of UXT disrupts centrosome structure, and siRNA-mediated knockdown of UXT leads to cell death, establishing UXT as a centrosomal component essential for cell viability. Immunofluorescence, co-immunoprecipitation with gamma-tubulin, siRNA knockdown, overexpression studies Molecular biology of the cell Medium 16221885
2007 UXT (specifically the V2 isoform) is expressed predominantly in the nucleus and interacts specifically with NF-κB inside the nucleus. UXT is recruited to the NF-κB enhanceosome upon stimulation and forms a dynamic complex with NF-κB. RNAi knockdown of UXT impairs NF-κB transcriptional activity, attenuates NF-κB-dependent gene expression, and sensitizes cells to TNF-alpha-induced apoptosis. Yeast two-hybrid, co-immunoprecipitation, RNAi knockdown, reporter assays, chromatin immunoprecipitation-like enhanceosome recruitment assays The Journal of cell biology High 17620405
2007 UXT interacts with the EVI1 transcriptional repressor through EVI1's repressor domain (Rp). Enforced UXT expression suppresses EVI1-induced cell transformation in Rat1 fibroblasts. Evi1 mutants lacking the UXT-binding site (Evi1Δ706-707) produce larger transformation colonies, indicating that endogenous UXT inhibits EVI1 biological activity. Yeast two-hybrid, colony formation assay, Evi1 deletion mutants, Rat1 fibroblast transformation assay The FEBS journal Medium 17635584
2007 When overexpressed, GFP-tagged UXT localizes progressively from extranuclear cytosol to punctate cytosolic dots to perinuclear aggregates, coinciding with aggregation of mitochondria and LRPPRC, leading to mitochondrial aggregation and cell death. UXT was identified as a component of mitochondria-associated LRPPRC complex. GFP-UXT overexpression, fluorescence microscopy, co-localization with mitochondria and LRPPRC In vitro cellular & developmental biology. Animal Low 17554592
2011 UXT-V1 isoform localizes in the cytoplasm (in contrast to nuclear V2) and is a component of the TNF receptor signaling complex. UXT-V1 binds TRAF2 and prevents TRADD from recruiting FADD, thereby blocking formation of the apoptotic complex II. UXT-V1 is a short-half-life protein whose degradation facilitates complex II formation in response to TNF treatment. Subcellular fractionation, co-immunoprecipitation, siRNA knockdown, cycloheximide chase, apoptosis assays Molecular biology of the cell High 21307340
2011 UXT-V1 is a novel TRAF3-binding protein that facilitates the interaction between TRAF3 and MAVS on mitochondria. The N-terminal TRAF-binding motif of UXT-V1 binds the C-terminal TRAF domain of TRAF3. UXT-V1 knockdown impairs virus-induced activation of NF-κB and IRF3, attenuates IFN-β induction, and blocks TRAF3 and TRADD recruitment to mitochondria upon virus infection. Co-immunoprecipitation, siRNA knockdown, reporter assays, mitochondrial fractionation, domain mapping Journal of immunology High 22131337
2012 EBV BGLF4 kinase phosphorylates UXT at Thr3. This phosphorylation interferes with the interaction between UXT and NF-κB, reducing NF-κB enhanceosome activity and downregulating NF-κB-dependent gene expression. Knockdown of UXT in EBV-positive NA cells induced spontaneous lytic cycle, demonstrating UXT is required for maintenance of EBV latency. Wild-type but not phosphorylation-deficient UXT enhanced lytic protein expression. In vitro kinase assay, site-directed mutagenesis (Thr3), co-immunoprecipitation, reporter assays, lentiviral shRNA knockdown Journal of virology High 22933289
2013 VHL interacts with UXT as identified by yeast two-hybrid and confirmed by GST pull-down and co-immunoprecipitation. UXT recruits VHL to the nucleus. VHL associates with the DNA-binding domain and hinge domain of AR and induces AR ubiquitination. VHL interaction with AR activates AR transactivation upon DHT treatment; VHL knockdown inhibits AR ubiquitination and decreases AR transcriptional activation. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, ubiquitination assay, AR reporter assay, siRNA knockdown The Biochemical journal Medium 23961993
2013 UXT interacts with SARM via yeast two-hybrid analysis. The two UXT isoforms have opposing effects on SARM-induced apoptosis: UXT-V1 co-expressed with SARM reduces caspase 8 activity, while UXT-V2 strongly increases caspase 8 activity and enhances SARM-induced apoptosis by activating the extrinsic pathway and depolarizing mitochondria. Yeast two-hybrid, caspase 8 activity assay, mitochondrial membrane potential assay, overexpression of isoforms FEBS letters Medium 24021647
2013 UXT associates with Foxp3 in the nucleus of human regulatory T cells, interacting with the proline-rich domain in the N-terminus of Foxp3. UXT knockdown in Treg cells results in a less-suppressive phenotype, affects nuclear localization stability of Foxp3, and downregulates Foxp3-related gene expression. Co-immunoprecipitation, domain mapping, siRNA knockdown, suppression functional assays, immunofluorescence European journal of immunology Medium 24136450
2015 UXT attenuates Notch signaling by binding to promoters of Notch-responsive genes and specifically interacting with the transactivation domain of the Notch intracellular domain (NICD), thereby impairing the interaction between NICD and the transcription factor RBP-Jκ. UXT knockdown in zebrafish results in shorter intersegmental vessels, loss of tip cell behavior, and impaired endothelial cell migration and division; blockade of Notch signaling rescues these defects. Co-immunoprecipitation, chromatin immunoprecipitation (promoter binding), siRNA/morpholino knockdown in zebrafish, reporter assays, rescue experiments Development High 25617435
2015 UXT binds MDMX and suppresses basal p53 activity. UXT-mediated p53 inhibition results in NF-κB activation leading to induction of glycolysis. UXT acts as an oncogene promoting cell proliferation in vitro and tumor progression in vivo in sarcoma cells. Co-immunoprecipitation (UXT–MDMX interaction), pathway reporter screen, siRNA knockdown, overexpression, xenograft tumor model Oncotarget Medium 25974965
2016 EZH1 physically interacts with UXT, and also with SUZ12 but not EED. Knockdown of EZH1 or SUZ12 impairs NF-κB target gene transcriptional activation induced by TNFα, similar to UXT knockdown. EZH1 and SUZ12 regulate recruitment of p65 and RNA Pol II to NF-κB target genes without affecting H3K27 methylation or p65 nuclear translocation, acting synergistically with UXT. Co-immunoprecipitation, siRNA knockdown, chromatin immunoprecipitation with next-generation sequencing, reporter assays Journal of cell science Medium 27127229
2017 UXT was identified as a LOX-PP interacting protein. UXT associates with estrogen receptor alpha (ER) and decreases ER transcriptional activity and target gene expression. LOX-PP interaction relocalizes UXT to the cytoplasm, promotes UXT ubiquitination, and decreases UXT stability via proteasomal degradation, releasing repression of ER transcriptional activity. Yeast two-hybrid, co-immunoprecipitation (UXT–ER, UXT–LOX-PP), proteasome inhibitor rescue, subcellular fractionation, ER reporter assays Journal of cellular biochemistry Medium 28106301
2018 Constitutive deletion of Uxt in mice is embryonic lethal. Conditional knockout of Uxt in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis, manifesting between 6 and 7 days post-partum before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates transcription of genes governing SSC self-renewal, differentiation, and meiosis. Conditional knockout mouse model, histology, gene expression analysis (RNA-seq), immunofluorescence PloS one High 29649254
2018 In prostate cells, URI is tightly bound to UXT; together they form a multiprotein complex acting as transcriptional repressors. URI regulates KAP1 through PP2A phosphatase activity, and the URI/UXT complex interacts with AR, KAP1, and PP2A. Co-immunoprecipitation, protein complex characterization Advances in experimental medicine and biology Low 30484154
2019 Prostate-specific conditional knockout of Uxt in mice led to a hyperplastic phenotype with prostate secretion fluid blockage and PIN by 4–6 months; doubly mutant Uxt/Pten mice developed more aggressive PIN. UXT depletion in prostate cancer cells increased retroelement expression (LINE-1, Alu) and retrotransposition activity, and accumulated DNA damage. Prostate-specific conditional knockout mouse, tissue microarray, retrotransposition assay, DNA damage markers Oncotarget Medium 30774773
2020 Conditional knockout of Uxt in Sertoli cells results in smaller testes, loss of germ cells in a subset of seminiferous tubules, and reduced transcription of genes involved in tight junctions of the blood-testis barrier (BTB). Tracer experiments and electron microscopy confirmed that the BTB is permeable in Sertoli-specific UXT KO animals. Sertoli cell-specific conditional knockout, gene expression analysis, tracer permeability assay, electron microscopy Biology of reproduction High 32678429
2020 Conditional knockout of Uxt in mice leads to retinal degeneration resembling retinitis pigmentosa, including progressive reduction of photoreceptors, increased apoptotic cells, and impaired ERG responses. Mechanistically, UXT suppresses photoreceptor apoptotic cell death by inhibiting autophagy through regulation of MTOR activity; UXT KO leads to enhanced autophagic flux and apoptosis. Conditional knockout mouse, ERG, TUNEL assay, autophagic flux measurement, MTOR activity assay, RNA-seq Autophagy High 32744119
2020 SCF(Fbxo7) E3 ubiquitin ligase mediates polyubiquitination of UXT-V2 (with both K48 and K63 linkages), promoting its proteasomal degradation. The Ubl domain of Fbxo7 contributes to interaction with UXT-V2. UXT-V1 also interacts with and is ubiquitinated by Fbxo7. FBXO7 knockdown causes UXT-V2 accumulation and enhanced NF-κB reporter activity; Fbxo7-ΔF-box overexpression protects UXT-V2 from degradation. Co-immunoprecipitation, in vitro and in vivo ubiquitination assay, cycloheximide chase, ubiquitin chain restriction analysis, siRNA knockdown, reporter assay Biochimica et biophysica acta. General subjects High 33010352
2021 UXT was identified as an interacting protein of p62/SQSTM1 via yeast two-hybrid. UXT binds both protein aggregates and the LB domain of p62, and forms oligomers that increase p62 clustering, promoting efficient targeting to protein aggregates and clearance via autophagy (aggrephagy). Ectopic expression of human UXT delays SOD1(A4V)-induced motor neuron degeneration in Xenopus; disruption of the UXT–p62 interaction suppresses this protection. Yeast two-hybrid, co-immunoprecipitation, in vitro aggregate binding assay, Xenopus in vivo model, UXT–p62 interaction disruption mutants Nature communications High 33782410
2021 UXT was identified as a novel TSG101 interaction partner associated with TSG101-containing cytoplasmic vesicles by co-immunoprecipitation. UXT depletion promoted TSG101 vesicle–lysosome association and elevated autophagic carrier flux, enhancing CEP55 degradation through the lysosome pathway upon TSG101 overexpression. UXT plays a role in late endosome/autophagosome–lysosome fusion. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, lysosome inhibitor experiments Biochemical and biophysical research communications Low 33486193
2021 UXT interacts with DNMT3b (confirmed by co-immunoprecipitation) and inhibits lncRNA MEG3 expression by recruiting DNMT3b to the MEG3 imprinting control region, promoting hypermethylation. This negatively regulates the MEG3/p53 axis to promote breast cancer cell proliferation and tumor growth in a DNMT3b-dependent manner. Co-immunoprecipitation, methylation-specific PCR, RNA immunoprecipitation, xenograft tumor model, siRNA knockdown Molecular therapy oncolytics Medium 35229028
2022 UXT interacts with STING1 upon DNA mimic or cGAMP stimulation and promotes STING1 degradation through selective macroautophagy. UXT facilitates the interaction between SQSTM1/p62 and STING1 to enhance autophagic degradation of STING1. In vivo, UXT deficiency leads to enhanced cGAS-STING1 signaling in a DNA-virus infection mouse model and a TMPD-induced murine lupus model. Co-immunoprecipitation, autophagy inhibitor experiments, conditional knockout mouse models (DNA-virus infection, TMPD-lupus), PBMC functional assays, RNA-seq Autophagy High 35543189
2023 UXT acts as a repressor of SENP1 expression. MYB upregulates SENP1 while inhibiting UXT expression. By repressing SENP1, UXT affects the global SUMO landscape; reduced UXT leads to increased SENP1 activity, decreased SUMOylation of MYB targets, and autoactivation of MYB. UXT was identified as a novel SENP1 interaction partner by mapping of SENP1 interaction partners. RNA-seq after MYB knockdown/rescue with SUMO mutants, interactome mapping of SENP1, gene expression analysis The Journal of biological chemistry Low 37468105
2025 UXT forms hexameric and higher-order oligomeric structures (via β-hairpin-mediated assembly of hexamers) that are essential for its function as an autophagy adaptor. The high-order oligomer of UXT is required for efficient clearance of SOD1(A4V) aggregates both in vitro and in vivo. Disruption of high-order oligomerization abolishes UXT's ability to promote aggregate clearance. In silico structural homology modeling, in vitro aggregate clearance assays, in vivo Xenopus model with oligomerization-disrupting mutants iScience Medium 40092611
2025 UXT-V2 restricts HSV-2 replication by facilitating K48-linked ubiquitination of the viral glycoprotein B (gB), targeting it for proteasomal degradation. UXT-V2 interacts with gB and recruits the E3 ligase TRIM21 to ubiquitinate gB. This anti-viral function is independent of UXT-V2's role in NF-κB regulation. Knockout/overexpression of UXT-V2, co-immunoprecipitation (UXT-V2–gB, UXT-V2–TRIM21), ubiquitination assay (K48 linkage), proteasome inhibitor rescue, viral replication assay Virologica Sinica Medium 40907749

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus. Molecular biology of the cell 74 11854421
2007 UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome. The Journal of cell biology 54 17620405
2004 ART-27, an androgen receptor coactivator regulated in prostate development and cancer. The Journal of biological chemistry 49 14711828
2022 UXT attenuates the CGAS-STING1 signaling by targeting STING1 for autophagic degradation. Autophagy 46 35543189
1999 Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue. Genomics 46 10087202
2012 Epstein-Barr virus BGLF4 kinase downregulates NF-κB transactivation through phosphorylation of coactivator UXT. Journal of virology 45 22933289
2005 UXT is a novel centrosomal protein essential for cell viability. Molecular biology of the cell 42 16221885
2016 The EZH1-SUZ12 complex positively regulates the transcription of NF-κB target genes through interaction with UXT. Journal of cell science 32 27127229
2017 UXT-AS1-induced alternative splicing of UXT is associated with tumor progression in colorectal cancer. American journal of cancer research 30 28401004
2005 Androgen receptor mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART-27 coactivator function. Molecular endocrinology (Baltimore, Md.) 30 15919721
2011 UXT-V1 facilitates the formation of MAVS antiviral signalosome on mitochondria. Journal of immunology (Baltimore, Md. : 1950) 27 22131337
2011 UXT-V1 protects cells against TNF-induced apoptosis through modulating complex II formation. Molecular biology of the cell 24 21307340
2021 UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy. Nature communications 23 33782410
2007 UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation. The FEBS journal 22 17635584
2021 UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis. Molecular therapy oncolytics 20 35229028
2007 UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation. In vitro cellular & developmental biology. Animal 20 17554592
2020 Mice deficient in UXT exhibit retinitis pigmentosa-like features via aberrant autophagy activation. Autophagy 19 32744119
2017 UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells. Journal of cellular biochemistry 19 28106301
2013 Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL. The Biochemical journal 19 23961993
2013 UXT plays dual opposing roles on SARM-induced apoptosis. FEBS letters 16 24021647
2015 UXT potentiates angiogenesis by attenuating Notch signaling. Development (Cambridge, England) 15 25617435
2015 UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity. Oncotarget 14 25974965
2020 The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway. Biochimica et biophysica acta. General subjects 11 33010352
2011 Alfa-class prefoldin protein UXT is a novel interacting partner of Amyotrophic Lateral Sclerosis 2 (Als2) protein. Biochemical and biophysical research communications 10 21907703
2013 UXT is a novel regulatory factor of regulatory T cells associated with Foxp3. European journal of immunology 9 24136450
2021 HOXD9 transcriptionally induced UXT facilitate breast cancer progression via epigenetic modification of RND3. Cellular signalling 7 34767964
2020 UXT in Sertoli cells is required for blood-testis barrier integrity†. Biology of reproduction 7 32678429
2019 Prostate-specific loss of UXT promotes cancer progression. Oncotarget 7 30774773
2018 UXT is required for spermatogenesis in mice. PloS one 7 29649254
2018 Role of the Unconventional Prefoldin Proteins URI and UXT in Transcription Regulation. Advances in experimental medicine and biology 6 30484154
2023 UXT at the crossroads of cell death, immunity and neurodegenerative diseases. Frontiers in oncology 4 37152054
2022 The role of UXT in tumors and prospects for its application in hepatocellular carcinoma. Future oncology (London, England) 4 36000398
2023 MYB regulates the SUMO protease SENP1 and its novel interaction partner UXT, modulating MYB target genes and the SUMO landscape. The Journal of biological chemistry 3 37468105
2021 Depletion of UXT, a novel TSG101 interaction protein, leads to enhanced CEP55 attenuation through lysosome degradation. Biochemical and biophysical research communications 1 33486193
2026 Ubiquitously expressed prefoldin-like chaperone (UXT) regulates putrescine metabolism and promotes colorectal cancer progression. Human cell 0 41931169
2025 UXT oligomerization is essential for its role as an autophagy adaptor. iScience 0 40092611
2025 UXT enhances melanoma proliferation, migration, and invasion through modulation of the P53 signaling pathway. Cell division 0 40462113
2025 Ubiquitously expressed transcript isoform 2 (UXT-V2) restricts HSV-2 replication by targeting glycoprotein B for degradation through ubiquitin-proteasome pathway. Virologica Sinica 0 40907749

Missed literature

Know a paper Affinage missed for UXT? Flag it for the maintainers and the community.

No submissions yet.