| 2013 |
UBXN1 inhibits RLR/MAVS-mediated antiviral signaling by binding to MAVS, interfering with MAVS oligomerization, and disrupting the MAVS/TRAF3/TRAF6 signalosome; UBXN1 is induced following viral infection and acts specifically on RNA-virus-induced (not TLR3, TLR4, or DNA-virus-induced) innate immune responses. |
Co-immunoprecipitation, siRNA knockdown, overexpression in cell lines, viral infection assays (VSV, Sendai, WNV, dengue); reporter assays for IFN induction |
Cell reports |
High |
23545497
|
| 2010 |
UBXN1 recognizes autoubiquitinated BRCA1 through a bipartite interaction: the UBA domain binds K6-linked polyubiquitin chains on BRCA1, while C-terminal sequences bind the BRCA1/BARD1 heterodimer in a ubiquitin-independent manner; UBXN1 binding dramatically reduces the E3 ligase activity of BRCA1/BARD1. |
Biochemical pulldown, Co-immunoprecipitation, in vitro ubiquitination assays, domain-mapping experiments with UBA and C-terminal UBXN1 fragments |
Molecular and cellular biology |
High |
20351172
|
| 2015 |
UBXN1 is a negative regulator of TNFα-triggered NF-κB signaling: it interacts with cIAP1 (an E3 ligase for RIP1 in the TNFR1 complex), competitively blocks cIAP1 recruitment to TNFR1, and thereby inhibits RIP1 polyubiquitination; this mechanism is independent of VCP/p97 (p97 knockdown does not affect UBXN1-mediated NF-κB inhibition). |
siRNA screen (51 ubiquitin-associated domain proteins), Co-immunoprecipitation, overexpression/knockdown, NF-κB reporter assays, RIP1 ubiquitination assays |
The Journal of biological chemistry |
High |
25681446
|
| 2010 |
UBXN1 (SAKS1) acts as a p97 adaptor that negatively modulates ERAD: it requires both polyubiquitin binding (UBA domain) and p97 binding (UBX domain) to function, and polyubiquitin binding positively regulates the SAKS1–p97 association; SAKS1 also protects polyubiquitin chains from deubiquitinase activity (e.g., ataxin-3), thereby slowing ERAD substrate degradation. |
In vitro binding assays, ERAD substrate degradation assays, p97 interaction studies, deubiquitinase protection assays |
The Journal of biological chemistry |
High |
21135095
|
| 2018 |
UBXN1 serves as the VCP adaptor in the BAG6 triage pathway: the VCP–UBXN1 complex recognizes ubiquitylated cytosolic proteins bound to the BAG6 complex prior to ER insertion (but not during ERAD); loss of VCP–UBXN1 causes inappropriate stabilization of ubiquitylated BAG6 clients and their accumulation in insoluble aggregates, sensitizing cells to proteotoxic stress. |
Co-immunoprecipitation, siRNA/KO cell lines, proteasomal degradation assays, protein aggregation/solubility fractionation, proteotoxic stress assays |
Molecular and cellular biology |
High |
29685906
|
| 2021 |
UBXN1 (SAKS1) is a VCP/p97 cofactor required for mitophagy initiation: upon mitochondrial depolarization and in a PRKN-dependent manner, UBXN1 translocates with VCP to mitochondria; UBXN1 physically interacts with PRKN via its UBX domain; loss of UBXN1 impairs VCP and PRKN recruitment to depolarized mitochondria, reduces mitophagic flux, and leads to accumulation of MFN2 in para-mitochondrial 'blobs', indicating UBXN1 facilitates MFN2 removal from the outer mitochondrial membrane downstream of PINK1. |
Live-cell imaging, mitochondrial fractionation, Co-immunoprecipitation (UBX-domain-dependent PRKN interaction), siRNA/KO cell lines, mitophagy flux assays, domain-mapping (UBX deletion) |
Autophagy |
High |
33966597
|
| 2021 |
UBXN1 is required for aggresome formation: UBXN1 is recruited to aggresomes upon proteasome inhibition; UBXN1-knockout cells cannot form aggresomes and show increased Huntingtin polyQ inclusion bodies in mammalian cells and in a C. elegans Huntington's disease model; the p97–UBXN1 complex mediates aggresome formation and clearance. |
KO cell lines, immunofluorescence/live imaging of aggresome formation, C. elegans genetic model, siRNA, proteasome inhibition assays |
Journal of cell science |
High |
33712450
|
| 2024 |
UBXN1 is a negative regulator of the unfolded protein response (UPR) and ER proteostasis: loss of UBXN1 activates the UPR, upregulates ER quality-control proteins, and increases translation in both resting and ER-stressed cells; this translational repression function is independent of p97. |
KO cell lines, quantitative proteomics, UPR reporter assays, translation assays, epistasis with p97 inhibition |
EMBO reports |
High |
38177917
|
| 2020 |
The extended UBA domain of UBXN1 specifically recognizes K6-linked diubiquitin: a C-terminally extended form of the UBA domain confers K6-linkage specificity, converging the two solution conformations of K6 diUb into a single conformation upon binding; the non-extended UBA domain does not show linkage preference. |
NMR spectroscopy with 15N-labeled synthetic diubiquitins, chemical shift perturbation, structural analysis |
Frontiers in chemistry |
High |
32039147
|
| 2016 |
UBA-UBX proteins p47 and SAKS1 (UBXN1) have opposing roles in ERAD substrate degradation: p47 promotes degradation of α-TCR while SAKS1 delays it; SAKS1 selectively inhibits degradation of ERAD substrates without affecting cytosolic proteasomal substrates; expression of SAKS1 is reduced in cells stably expressing ERAD substrates and elevated upon ER stress. |
ERAD substrate degradation assays (α-TCR, α1-antitrypsin, δCD3), siRNA knockdown, pulse-chase/cycloheximide chase, stable cell lines expressing ERAD substrates |
Molecular and cellular biochemistry |
Medium |
27785701
|
| 2024 |
UBXN1 promotes noncanonical inflammasome activation: together with unanchored K48/K63-linked polyubiquitin chains, UBXN1 binds caspase-4/11, promoting their assembly and activation; UBXN1 deficiency impairs caspase-4/11 activation, cytokine secretion, and pyroptosis in response to intracellular LPS; UBXN1-deficient mice are protected from LPS- and CLP-induced sepsis. |
Co-immunoprecipitation (UBXN1–caspase-4/11 interaction), KO cell lines and mice, inflammasome activation assays, recombinant USP5 depletion of unanchored polyUb, USP5 inhibitor experiments |
bioRxivpreprint |
Medium |
bio_10.1101_2024.10.30.621131
|
| 2024 |
UBR5 mediates Lys11-linked polyubiquitination and degradation of UBXN1 downstream of SUB1/PC4, thereby activating NF-κB signaling; SUB1 interacts with UBR5 and increases its protein level, leading to reduced UBXN1 and consequently elevated NF-κB activity. |
Co-immunoprecipitation (SUB1–UBR5 interaction), ubiquitination assays (Lys11 linkage), KO/knockdown, NF-κB reporter assays, in vivo tumor models |
Science China. Life sciences |
Medium |
38240906
|
| 2021 |
YTHDF2 accelerates UBXN1 mRNA degradation via METTL3-mediated m6A modification, leading to reduced UBXN1 protein and consequent NF-κB activation; UBXN1 overexpression attenuates the oncogenic effect of YTHDF2 overexpression. |
RNA immunoprecipitation (RIP), methylated RIP (MeRIP), RNA stability assays, siRNA knockdown/overexpression, orthotopic xenograft models |
Journal of hematology & oncology |
Medium |
34246306
|
| 2021 |
The lncRNA PRADX recruits the PRC2/DDX5 complex to the UBXN1 gene promoter, increasing H3K27 trimethylation and suppressing UBXN1 transcription, which in turn promotes NF-κB activity. |
ChIRP (chromatin isolation by RNA purification), ChIP, Co-IP, siRNA knockdown, H3K27me3 ChIP at UBXN1 promoter, xenograft models |
Theranostics |
Medium |
33754075
|
| 2024 |
UBXN1 interacts with the inner mitochondrial membrane protein prohibitin (PHB) and sustains PHB expression; UBXN1 inhibition triggers mitochondrial damage and HCC cell apoptosis, indicating a role in maintaining mitochondrial homeostasis. |
Co-immunoprecipitation (UBXN1–PHB), KO/knockdown, apoptosis assays (TUNEL, FACS), mouse liver tumor models (Sleeping Beauty transposon) |
Journal of translational medicine |
Medium |
38773518
|
| 2019 |
UBXN1 interacts with the TGEV coronavirus S1 spike protein and positively supports viral replication; UBXN1 knockdown reduces viral titer and S1 expression while overexpression increases viral copy number; UBXN1 negatively regulates IFN-β expression after TGEV infection. |
Yeast two-hybrid, GST pulldown, Co-immunoprecipitation, siRNA knockdown, overexpression, viral titer assays |
Veterinary research |
Low |
31029162
|