Affinage

UCHL1

Ubiquitin carboxyl-terminal hydrolase isozyme L1 · UniProt P09936

Length
223 aa
Mass
24.8 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 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

UCHL1 is a neuronal-abundant, cysteine/histidine-dependent ubiquitin C-terminal hydrolase whose catalytic activity maintains free ubiquitin homeostasis and supports neuronal and synaptic integrity (PMID:8809066, PMID:36216817, PMID:11555633). Biochemically it is a deubiquitinating enzyme distinguishable from its homologue UCH-L3 by distinct substrate recognition, and structural work captures it in a hybrid conformation between apo and ubiquitin-bound states whose inhibition lowers cellular monoubiquitin, phenocopying genetic inactivation (PMID:17144664, PMID:36216817). Genetic loss of UCHL1 alone or together with UCH-L3 produces progressive axonal degeneration, and selective motor axon and neuromuscular-junction failure, establishing its role in neuronal maintenance rather than neuron survival (PMID:11555633, PMID:27231703). Across many cell types UCHL1 acts as a substrate-stabilizing DUB: it deubiquitinates and stabilizes TrkB to sustain BDNF signaling and memory, EGFR to drive cardiac hypertrophy and ER-negative breast cancer, HIF-1α after myocardial infarction, AKT1 in pulmonary hypertension, and metabolic and trafficking substrates including PKM, PFKFB3, CD36, CD13, POM121, Sox17, and FDXR (PMID:28500221, PMID:32494592, PMID:32042339, PMID:35339825, PMID:38695173, PMID:34244144, PMID:40016338, PMID:32801299, PMID:39389988, PMID:38244540, PMID:38478109, PMID:38081437). Through these substrates UCHL1 regulates glycolytic reprogramming, mitophagy, mTOR complex balance, and endothelial barrier and angiogenic function (PMID:34244144, PMID:23297343, PMID:38478109, PMID:33438509). It also restrains necroptosis by stabilizing RIPK1/RIPK3, modulates NF-κB and NLRP3 inflammasome signaling in myeloid cells, and promotes MHC class I recycling for dendritic-cell cross-presentation (PMID:31247189, PMID:34288216, PMID:38669140, PMID:31492742). Its catalytic activity is itself a regulated node: the active-site cysteine C152 is inactivated by ischemia-generated reactive lipids, and hydrolase-dead knock-in mice show worsened axonal injury after trauma, linking loss of UCHL1 catalysis to impaired ubiquitin-proteasome function (PMID:30760601, PMID:33159930).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 1996 High

    Established the biochemical identity of UCHL1 as a catalytic enzyme, defining the mechanistic basis for all subsequent functional work.

    Evidence Affinity purification of native PGP9.5/UCH-L1 from bovine retina with enzymatic and active-site reagent characterization

    PMID:8809066

    Open questions at the time
    • Cellular substrates not addressed
    • Physiological role undefined
  2. 2001 High

    Answered whether UCHL1 is required for neuronal maintenance by showing genetic loss causes axonal degeneration with partial redundancy to UCH-L3.

    Evidence Uch-L1/Uch-L3 double-knockout mice with histological axonal phenotyping

    PMID:11555633

    Open questions at the time
    • Molecular substrates driving degeneration not identified
    • Mechanism of redundancy unresolved
  3. 2002 Medium

    First interactor work linking UCHL1 to cell-cycle control via JAB1 and p27Kip1 in a nuclear complex.

    Evidence Yeast two-hybrid, reciprocal Co-IP and colocalization in lung cancer cells

    PMID:12082530

    Open questions at the time
    • No reconstituted degradation assay
    • Direct DUB activity on p27Kip1 not shown
  4. 2006 High

    Demonstrated that UCHL1 enzymatic activity is functionally required for synaptic plasticity and memory, connecting its DUB activity to PKA/CREB signaling.

    Evidence TAT-UCH-L1 transduction and rescue in hippocampal slices and APP/PS1 mice with behavioral readout

    PMID:16923396

    Open questions at the time
    • Direct synaptic substrate not identified
    • Mechanism linking DUB activity to PKA-RIIalpha unclear
  5. 2006 High

    Defined the mechanistic basis of UCHL1 substrate specificity distinct from UCH-L3 at the level of Michaelis-complex formation.

    Evidence In vitro kinetics with a ubiquitin fusion panel

    PMID:17144664

    Open questions at the time
    • Physiological substrates not tested
    • No structural correlate at the time
  6. 2008 Medium

    Connected PD-associated and oxidatively damaged UCHL1 to a gain of aberrant tubulin interaction, providing a toxicity mechanism.

    Evidence Circular dichroism, solubility fractionation, tubulin pulldown and polymerization assays in transgenic mice

    PMID:18250096

    Open questions at the time
    • Single lab
    • Causal link to neurodegeneration in vivo incomplete
  7. 2013 High

    Revealed that UCHL1 reorganizes mTOR complex balance by counteracting DDB1-CUL4-mediated raptor ubiquitination, shifting activity from mTORC1 to mTORC2.

    Evidence Co-IP, ubiquitination assays and genetic mouse models with kinase activity readouts

    PMID:23297343

    Open questions at the time
    • Whether raptor is a direct DUB substrate vs ligase disruption not fully separated
  8. 2013 Medium

    Established UCHL1 as a pro-necroptotic factor activated by monoubiquitination during TNF-induced caspase-independent death.

    Evidence RNAi and pharmacological inhibition with monoubiquitination detection in podocytes

    PMID:24090154

    Open questions at the time
    • Direct necroptotic substrate not identified in this study
    • Single lab
  9. 2013 Medium

    Defined transcriptional control of UCHL1 by NF-κB, embedding it in inflammatory signaling loops.

    Evidence EMSA, promoter reporter and NF-κB inhibition in cytokine-stimulated podocytes

    PMID:23567262

    Open questions at the time
    • Other transcriptional regulators not excluded
  10. 2014 Medium

    Showed UCHL1 stabilizes cytoplasmic p27Kip1 by promoting nuclear export and reducing its ubiquitination, driving podocyte hypertrophy.

    Evidence Gain/loss of function with fractionation and ubiquitination assays in podocytes and disease tissue

    PMID:24583340

    Open questions at the time
    • Direct vs indirect deubiquitination of p27Kip1 not resolved
  11. 2017 High

    Identified TrkB as a direct UCHL1 substrate, explaining how UCHL1 sustains BDNF signaling and memory by preventing receptor degradation.

    Evidence In vitro deubiquitination, K460 site mapping and competitive peptide with in vivo behavioral readout

    PMID:28500221

    Open questions at the time
    • Recruitment of UCHL1 to TrkB unclear
  12. 2016 Medium

    Linked UCHL1 activity to tau microtubule binding and phosphorylation, implicating it in cytoskeletal/aggregation pathways.

    Evidence Inhibitor and siRNA in neuronal cells with tau-microtubule binding assays

    PMID:26444754 PMID:28540657

    Open questions at the time
    • Whether tau is a direct substrate not shown
    • K63-chain mechanism via HDAC6 single lab
  13. 2015 Medium

    Connected UCHL1 to excessive mitophagy when aberrantly recruited to mitochondria by an N-terminal tau fragment.

    Evidence shRNA silencing with mitophagy and viability assays plus human AD synaptic mitochondria Co-IP

    PMID:25687137

    Open questions at the time
    • Mechanism of mitochondrial recruitment unresolved
  14. 2018 High

    Showed UCHL1 promotes eIF4F assembly and protein synthesis independent of mTORC1, a catalytic-activity-dependent route required for MYC-driven lymphoma.

    Evidence BioID, Co-IP, protein synthesis assays and catalytic-mutant mice in Eu-myc model

    PMID:30257881

    Open questions at the time
    • Direct DUB substrate within eIF4F not pinpointed
  15. 2019 Medium

    Extended mTOR-balance regulation to skeletal muscle, with PRAS40 turnover as a contributing node.

    Evidence Muscle-specific knockout and C2C12 knockdown with mTORC1/2 readouts

    PMID:31356902

    Open questions at the time
    • Fiber-type selectivity mechanism unexplained
  16. 2019 Medium

    Defined a role in dendritic-cell cross-presentation by promoting MHC class I recycling rather than uptake or phagosome maturation.

    Evidence UCHL1-deficient mice with cross-priming, recycling and colocalization assays

    PMID:31492742

    Open questions at the time
    • Molecular substrate controlling recycling not identified
  17. 2019 Medium

    Established UCHL1 maintenance of endothelial barrier integrity via junctional protein expression and a FoxO1 axis.

    Evidence siRNA and LDN-57444 with TEER, junction protein blots, FoxO1 rescue and VILI model

    PMID:33438509

    Open questions at the time
    • Direct substrate linking UCHL1 to claudin-5/FoxO1 unknown
  18. 2019 Medium

    Identified RIPK1/RIPK3 as stability-dependent effectors through which UCHL1 promotes podocyte necroptosis.

    Evidence siRNA with protein half-life and MLKL activation assays plus diabetic nephropathy model

    PMID:31247189

    Open questions at the time
    • Direct deubiquitination of RIPK1/RIPK3 not formally demonstrated
  19. 2019 High

    Determined that ischemia-generated reactive lipids inactivate UCHL1 at C152, identifying a stroke-relevant post-translational off-switch.

    Evidence C152A knock-in mice with MCAO, electrophysiology and behavior

    PMID:30760601

    Open questions at the time
    • Identity of all relevant lipid adducts not catalogued
  20. 2020 High

    Identified EGFR as a UCHL1 substrate driving pathological cardiac hypertrophy and, separately, ERα suppression in breast cancer.

    Evidence Reciprocal Co-IP, ubiquitination assays, in vivo cardiac and xenograft models, pharmacological inhibition

    PMID:32042339 PMID:32494592

    Open questions at the time
    • Selectivity of UCHL1 among receptor pools unclear
  21. 2020 Medium

    Showed UCHL1 stabilizes CD36 to promote oxLDL uptake and foam-cell formation.

    Evidence siRNA, inhibitor and CD36 ubiquitination assays with lipid uptake readout

    PMID:32801299

    Open questions at the time
    • Single lab
    • In vivo atherosclerosis confirmation limited
  22. 2020 High

    Demonstrated hydrolase activity per se is required for axonal protection after TBI via maintenance of proteasome function.

    Evidence C90A hydrolase-dead knock-in mice in controlled cortical impact model

    PMID:33159930

    Open questions at the time
    • Specific accumulated substrates after TBI not defined
  23. 2021 High

    Connected UCHL1 to glycolysis/mitophagy via PKM stabilization, with TRIM63 as the antagonist E3 ligase, mitigating PD-related phenotypes.

    Evidence Knockout cells and Drosophila, PKM stability assays, AMPK/mitophagy readouts and E3 identification

    PMID:34244144

    Open questions at the time
    • Generality across neuronal subtypes untested
  24. 2021 Medium

    Defined an anti-inflammatory role through stabilization of IκBα and restraint of NF-κB in macrophages.

    Evidence Co-IP, ubiquitination assay, inhibitor and in vivo LPS model

    PMID:34288216

    Open questions at the time
    • Apparent context-dependence vs pro-inflammatory roles unreconciled
  25. 2021 Medium

    Showed UCHL1 sustains proteostasis in ovarian cancer through a PSMA7-APEH-proteasome axis supporting mTORC1 and protein synthesis.

    Evidence siRNA, sequential knockdown, proteasome activity and UPR assays with xenograft

    PMID:33753553

    Open questions at the time
    • Direct DUB substrate within the axis not identified
  26. 2022 High

    Provided the crystal structure of UCHL1 with a stereoselective inhibitor, defining a hybrid conformational state and validating monoubiquitin readout of activity.

    Evidence X-ray crystallography, activity-based probes and cellular monoubiquitin measurement

    PMID:36216817

    Open questions at the time
    • Substrate-bound full catalytic cycle structure not captured
  27. 2022 Medium

    Identified HIF-1α stabilization by UCHL1 as cardioprotective after myocardial infarction.

    Evidence BioID-MS, CRISPR knockout hiPSC cardiomyocytes and AAV9 delivery in MI model

    PMID:35339825

    Open questions at the time
    • Single lab
    • Direct vs indirect HIF-1α regulation not fully separated
  28. 2023 High

    Defined dual osteoclast-regulatory mechanisms: TAZ stabilization at K46 to inhibit NFATC1, suppressing osteoclastogenesis.

    Evidence Osteoclast-specific knockout, K46 mutagenesis, reconstituted deubiquitination and NFATC1 transport assays

    PMID:37215988

    Open questions at the time
    • Interplay with other osteoclast substrates unresolved
  29. 2023 Medium

    Identified POM121 as a UCHL1 substrate controlling E2F1/c-MYC nuclear transport in neuroendocrine cancers.

    Evidence Co-IP, deubiquitination and nuclear fractionation assays with in vivo models

    PMID:38244540

    Open questions at the time
    • Single lab
    • Selectivity for POM121 among nucleoporins unclear
  30. 2023 Medium

    Linked UCHL1 to mitochondrial iron homeostasis and inflammasome control via FDXR stabilization during HCMV infection.

    Evidence Co-IP, ubiquitination assay, knockdown and MCMV-infected mice

    PMID:38081437

    Open questions at the time
    • Single lab
    • How infection lowers UCHL1 not detailed
  31. 2024 High

    Established UCHL1 as a driver of pulmonary arterial hypertension through AKT1 stabilization via ubiquitin chain editing.

    Evidence Knockout rats, conditional mouse KO, siRNA, inhibitor and K63/K48 ubiquitination assays across three PAH models

    PMID:38695173

    Open questions at the time
    • Mechanism of chain-type switching unresolved
  32. 2024 Medium

    Defined UCHL1 interaction with the NLRP3 NACHT domain and its requirement for inflammasome assembly in microglia.

    Evidence Proximity labeling, Co-IP, puncta/ASC oligomerization imaging and chemical inhibition

    PMID:38669140

    Open questions at the time
    • Whether NLRP3 is a catalytic substrate not established
  33. 2024 High

    Showed UCHL1 stabilizes CD13 in osteoclast precursors to generate an autocrine MAPK-inhibitory signal that suppresses osteoclastogenesis in osteoarthritis.

    Evidence Conditional KO and AAV9 overexpression, CD13 ubiquitination assay and MAPK analysis in two species

    PMID:39389988

    Open questions at the time
    • Relationship to TAZ/NFATC1 osteoclast pathway not integrated
  34. 2024 Medium

    Demonstrated UCHL1 stabilization of Sox17 supports endothelial angiogenesis and barrier recovery after spinal cord injury.

    Evidence IP-MS, Co-IP, conditional KO mice and endothelial functional assays

    PMID:38478109

    Open questions at the time
    • Single lab
    • Ubiquitination site on Sox17 not mapped
  35. 2025 Medium

    Revealed a UCHL1/PFKFB3 glycolytic feedback loop sustained by histone lactylation that protects neurons from ferroptosis after spinal cord injury.

    Evidence Genetic deletion, K48 ubiquitination and histone lactylation assays with scRNA-seq and SCI model

    PMID:40016338

    Open questions at the time
    • Single lab
    • Generality of lactylation feedback beyond astrocytes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UCHL1 achieves substrate selectivity across its many reported targets and is directed to opposing pro- versus anti-inflammatory and pro- versus anti-survival outcomes in different cell types remains unresolved.
  • No unifying model for substrate recruitment
  • Context-dependent functional switching mechanism unknown
  • Most substrate interactions documented in single labs

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AKT1EGFRHIF1ANLRP3PKMRIPK1RIPK3TRKB
Complex memberships
NLRP3 inflammasomeeIF4FmTORC1mTORC2

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 UCH-L1 deubiquitinating activity is required for normal synaptic and cognitive function; restoration of UCH-L1 enzymatic activity (via TAT-UCH-L1 fusion protein) rescues beta-amyloid-induced decreases in synaptic function and restores normal levels of PKA-regulatory subunit IIalpha, PKA activity, and CREB phosphorylation in hippocampal slices and APP/PS1 mice. TAT-fusion protein transduction into hippocampal slices and APP/PS1 mice; enzymatic activity assays; biochemical measurement of PKA-RIIalpha, PKA activity, and CREB phosphorylation; contextual fear conditioning Cell High 16923396
2002 UCH-L1 (PGP9.5) interacts with JAB1 (a Jun activation domain-binding protein involved in p27Kip1 degradation) in vitro and in vivo, and both proteins form a heteromeric complex with p27Kip1 in the nucleus of lung cancer cells; nuclear translocation of UCH-L1 and JAB1 coincides with reduced nuclear p27Kip1 levels, suggesting UCH-L1 contributes to p27Kip1 degradation via JAB1. Yeast two-hybrid screen; co-immunoprecipitation in vitro and in vivo; colocalization studies; serum restimulation and contact inhibition experiments Oncogene Medium 12082530
2013 UCH-L1 regulates the balance between mTORC1 and mTORC2 by disrupting the DDB1-CUL4 ubiquitin ligase complex interaction with raptor and counteracting DDB1-CUL4-mediated raptor ubiquitination, leading to mTORC1 dissolution and secondary increase in mTORC2 activity (increased Akt phosphorylation, decreased S6K and 4EBP1 phosphorylation). Co-immunoprecipitation; ubiquitination assays; mTOR complex assembly analysis; UCHL1-deficient and transgenic mouse models; kinase activity assays for S6K, 4EBP1, and Akt Molecular and cellular biology High 23297343
2008 Familial PD-associated I93M mutant UCH-L1 and carbonyl-modified (oxidatively damaged) UCH-L1 share aberrant properties: increased insolubility, elevated interactions with multiple proteins including tubulin, and similar structural changes by circular dichroism; aberrant interaction of mutant or carbonyl-modified UCH-L1 with tubulin modulates tubulin polymerization. Circular dichroism analysis; solubility fractionation; co-immunoprecipitation/pulldown with tubulin; in vitro tubulin polymerization assay; transgenic mice Human molecular genetics Medium 18250096
2018 UCH-L1 associates with and promotes assembly of the translation initiation complex eIF4F and stimulates protein synthesis through a mechanism requiring its catalytic (deubiquitinase) activity; this bypasses mTORC1-dependent protein synthesis and is required for MYC-driven lymphomagenesis in Eμ-myc mice. Proximity-based proteomics (BioID); co-immunoprecipitation; protein synthesis assays; catalytic mutant UCH-L1 transgenic mice; Eμ-myc lymphoma model Blood High 30257881
2006 UCH-L1 displays distinct substrate recognition from its homologue UCH-L3; specific ubiquitin side chains critical for forming the Michaelis complex and enabling catalysis by UCH-L1 were identified using a panel of ubiquitin fusions; activation parameters show mechanistic differences in substrate specificity between UCH-L1 and UCH-L3. In vitro enzymatic assays with ubiquitin fusion panel; kinetic analysis; activation parameter measurements Biochemistry High 17144664
2022 Crystal structure of UCHL1 in complex with inhibitor GK13S reveals the enzyme locked in a hybrid conformation between apo and ubiquitin-bound states; stereoselective inhibition of cellular UCHL1 by GK13S reduces monoubiquitin levels in glioblastoma cells, phenocopying an inactivating mouse mutation of UCHL1. X-ray crystallography; biochemical characterization of activity-based probes; cellular monoubiquitin measurement; activity-based probe labeling Nature communications High 36216817
2017 UCH-L1 directly deubiquitinates TrkB (the BDNF receptor) at lysine K460 in the juxtamembrane domain; UCH-L1-regulated TrkB deubiquitination prevents BDNF-induced TrkB internalization and lysosomal degradation, sustaining surface TrkB levels, TrkB activation, and downstream signaling; blocking UCH-L1–TrkB interaction in vivo impairs hippocampus-dependent memory. Co-immunoprecipitation; in vitro deubiquitination assay; ubiquitination site mapping (K460); competitive inhibitory peptide; in vivo hippocampal injection and fear conditioning The Journal of neuroscience High 28500221
2020 UCHL1 binds, deubiquitinates, and stabilizes EGFR (epidermal growth factor receptor), thereby activating downstream EGFR mediators and driving pathological cardiac hypertrophy; knockdown of UCHL1 ameliorates hypertrophy while overexpression exacerbates it. Co-immunoprecipitation; ubiquitination assay; UCHL1 knockdown and overexpression in cardiomyocytes; rAAV9-UCHL1 mouse model; pressure overload model; pharmacological inhibition with LDN-57444 Science advances High 32494592
2020 UCHL1 deubiquitinates and stabilizes EGFR, which suppresses ERα transcription, thereby downregulating estrogen receptor alpha expression in breast cancer; UCH-L1 inhibition restores ERα expression and sensitizes ER-negative breast cancer to tamoxifen and fulvestrant in vivo and in vitro. Immunoprecipitation; ubiquitination assay; luciferase reporter; ChIP assay; qRT-PCR; immunoblotting; in vivo xenograft model Theranostics Medium 32042339
2013 UCH-L1 protects from TNF-induced necroptosis; HtrA2/Omi serine protease induces monoubiquitination of UCH-L1 (indicative of activation) during necroptosis rather than cleaving it; pharmacological or RNAi-mediated inhibition of UCH-L1 protects cells from TNF-induced necroptosis; UCH-L1 is a mediator of caspase-independent cell death in kidney podocytes. Pharmacological inhibition; RNA interference; cell death assays; monoubiquitination detection; PARP-1 cleavage; caspase activity assays; morphological analysis Cell communication and signaling : CCS Medium 24090154
2019 UCHL1 promotes podocyte necroptosis by maintaining deubiquitinated (stabilized) RIPK1 and RIPK3; UCHL1 knockdown reduces half-life and expression of RIPK1 and RIPK3, decreasing MLKL activation and protecting podocytes from high-glucose-induced necroptosis. UCHL1 siRNA knockdown; protein half-life assay; Western blot for RIPK1, RIPK3, MLKL, caspase-3; cell death assays; scanning electron microscopy; in vivo diabetic nephropathy model Experimental cell research Medium 31247189
2019 Binding of ischemia-induced reactive lipid species to cysteine C152 of UCHL1 inactivates the enzyme; a C152A knock-in mouse resistant to lipid adduction showed decreased axonal injury, reduced tissue loss, preserved excitatory synaptic drive and axonal conduction velocity, and improved sensorimotor recovery after MCAO, demonstrating that C152 is a key site for post-translational inactivation of UCHL1 by reactive lipids after stroke. C152A knock-in mouse; middle cerebral artery occlusion (MCAO); histological analysis; electrophysiology; behavioral assessment; polyubiquitinated protein detection Proceedings of the National Academy of Sciences of the United States of America High 30760601
2020 UCHL1 deubiquitinates and stabilizes pyruvate kinase (PKM), promoting glycolysis; loss of UCHL1 destabilizes PKM, reduces pyruvate and ATP levels, activates AMPK, and promotes AMPK-dependent mitophagy via ULK1 and FUNDC1, mitigating PD-related phenotypes caused by PINK1/Parkin loss-of-function. TRIM63 is identified as the E3 ligase for PKM, antagonizing UCHL1. UCHL1 knockout cells and Drosophila models; PKM stability assay; ATP/pyruvate measurements; AMPK activity assay; mitophagy assays; co-immunoprecipitation; E3 ligase identification Science advances High 34244144
2017 UCH-L1 interacts with and promotes K63-linked ubiquitin chain formation on tau, and its inhibition reduces K63-linked ubiquitin chains, decreases HDAC6 deacetylase activity, attenuates HDAC6–tau interaction, and impairs proteasomal impairment-induced tau aggresome formation. UCH-L1 inhibitor (LDN); UCH-L1 siRNA; immunoprecipitation; ubiquitin chain-linkage analysis; HDAC6 activity assay; tau aggresome immunofluorescence Molecular neurobiology Medium 28540657
2016 UCH-L1 inhibition decreases the microtubule-binding ability of tau and increases tau phosphorylation and abnormal ubiquitination; both pharmacological inhibition of UCH-L1 activity (LDN) and siRNA-mediated knockdown produce these effects in neuronal cell lines. UCH-L1 inhibitor LDN; UCH-L1 siRNA in HEK293/tau441 cells; tau-microtubule binding assay; immunofluorescence; immunoprecipitation; phosphorylation analysis Journal of Alzheimer's disease : JAD Medium 26444754
2012 UCHL1 interacts with NCAM180 (and NCAM140) isoforms of the neural cell adhesion molecule; overexpression of UCHL1 decreases constitutive ubiquitination of NCAM180 and NCAM140 and reduces their lysosomal localization, indicating UCHL1 regulates NCAM ubiquitination and intracellular trafficking/recycling. Protein macroarray screening; co-immunoprecipitation; colocalization in primary neurons; UCHL1 overexpression and inhibition; ubiquitination assays; lysosomal trafficking assays The FEBS journal Medium 23061666
2015 UCHL-1 is aberrantly recruited to mitochondria by NH2-terminal tau fragment (NH2htau) in neurons; shRNA-mediated silencing of UCHL-1 (or Parkin) suppresses excessive mitophagy induced by NH2htau, restores synaptic and mitochondrial content, and provides partial protection against NH2htau-induced neuronal death; endogenous NH2htau is associated with UCHL-1 and Parkin in mitochondria from human AD synapses. shRNA silencing of UCHL-1; mitophagy assays; mitochondrial fractionation; co-immunoprecipitation from human AD synaptic mitochondria; cell viability assays; primary hippocampal neurons Human molecular genetics Medium 25687137
2020 UCHL1 deubiquitinates CD36 (a scavenger receptor), stabilizing it and promoting oxidized LDL uptake and foam cell formation; UCHL1 inhibition or deletion increases K48-polyubiquitination of CD36 and reduces its protein levels, decreasing lipid accumulation. UCHL1 siRNA; UCHL1 inhibitor; ubiquitination assay for CD36; Western blot; lipid uptake assays Cell death & disease Medium 32801299
2021 UCHL1 interacts with IκBα protein and inhibits its K48-linked ubiquitination and proteasomal degradation; UCHL1 inhibition blocks LPS-induced IκBα degradation, suppresses NF-κB nuclear translocation, reduces ERK1/2 phosphorylation, and decreases pro-inflammatory cytokine production in macrophages. Co-immunoprecipitation; ubiquitination assay; UCHL1 inhibitor; Western blot for IκBα, phospho-ERK1/2, NF-κB; ELISA for IL-6 and TNF-α; in vivo LPS model Cell biology international Medium 34288216
2019 UCHL1 regulates mTORC1 and mTORC2 balance in skeletal muscle; skeletal muscle-specific knockout of UCHL1 increases mTORC1 activity and decreases mTORC2 activity in slow-twitch (soleus) but not fast-twitch (EDL) muscle, leading to enlarged slow-twitch muscle fibers; UCHL1 knockdown decreases PRAS40 protein turnover, contributing to increased mTORC1 activity. Skeletal muscle-specific UCHL1 knockout mice; C2C12 siRNA knockdown; mTORC1/2 activity assays (phosphorylation of downstream targets); fiber type staining; PRAS40 protein turnover assay Life sciences Medium 31356902
2020 UCHL1 hydrolase activity is required for normal axonal conduction and protection after traumatic brain injury; C90A knock-in mice (devoid of hydrolase activity) show increased axonal injury, greater hippocampal neuron loss, elevated polyubiquitinated proteins and Beclin-1 after controlled cortical impact, suggesting the hydrolase activity maintains UPS function and suppresses autophagy after TBI. C90A hydrolase-dead knock-in mouse; controlled cortical impact TBI model; histology; immunohistochemistry for APP and SMI-32; polyubiquitin and Beclin-1 Western blot; behavioral beam balance test Experimental neurology High 33159930
2024 UCHL1 interacts with the NACHT domain of NLRP3 inflammasome; UCH-L1 downregulation decreases pro-IL-1β levels; pharmacological UCH-L1 inhibition interferes with NLRP3 puncta formation and ASC oligomerization, reducing IL-1β cleavage and secretion particularly in microglia. Proximity labeling (affinity purification); RNAi screening; co-immunoprecipitation; NLRP3 puncta imaging; ASC oligomerization assay; UCHL1 chemical inhibition; IL-1β ELISA Cell reports Medium 38669140
2001 Uch-L1 and Uch-L3 have both separate and overlapping functions in maintaining axonal integrity: double Uch-L1/Uch-L3 knockout mice display earlier lethality, dysphagia, and more severe axonal degeneration of the gracile tract, nucleus tractus solitarius, and area postrema than either single knockout, demonstrating redundant and distinct roles in neuronal maintenance. Uch-L1/Uch-L3 double-knockout mouse generation; histological analysis of axonal degeneration; behavioral and survival analysis Human molecular genetics High 11555633
2024 UCHL1 deubiquitinates and stabilizes Sox17 in endothelial cells; conditional UCHL1 knockout impairs endothelial cell proliferation, migration, tube formation, angiogenesis, and blood-spinal cord barrier recovery after spinal cord injury, while UCHL1 overexpression promotes these processes. Immunoprecipitation-mass spectrometry; co-immunoprecipitation; conditional UCHL1 knockout mice; Sox17 knockdown/overexpression; in vitro endothelial cell assays; in vivo SCI model Cellular and molecular life sciences : CMLS Medium 38478109
2025 UCHL1 stabilizes PFKFB3 (a glycolytic regulator) in astrocytes by cleaving K48-linked ubiquitin chains; UCHL1/PFKFB3 axis increases lactate production, leading to histone H4K8 lactylation and subsequent transcriptional upregulation of Uchl1 and glycolysis genes, forming a positive feedback loop that sustains astrocytic glycolytic reprogramming and prevents neuronal ferroptosis after spinal cord injury. Genetic Uchl1 deletion; PFKFB3 knockout; K48-linked ubiquitination assay; histone lactylation assay; co-immunoprecipitation; scRNA-seq analysis; in vivo SCI model Cell death and differentiation Medium 40016338
2024 RANKL stimulates UCHL1 expression in osteoclast precursors; UCHL1 stabilizes CD13 (deubiquitinates it), augmenting soluble CD13 (sCD13) release, which exerts an autocrine inhibitory effect on the MAPK pathway to suppress osteoclast formation; conditional UCHL1 deletion in osteoclast precursors exacerbates OA while overexpression alleviates it. Conditional UCHL1 knockout mice; AAV9-UCHL1 overexpression; osteoclast differentiation assays; co-immunoprecipitation; ubiquitination assay for CD13; MAPK pathway analysis; human and murine OA specimens Nature communications High 39389988
2023 UCHL1 deubiquitinates and stabilizes TAZ at K46 (removing K48-linked polyubiquitin); stabilized TAZ competes with calcineurin A (CNA) for binding to NFATC1, inhibiting NFATC1 dephosphorylation and nuclear transport, thereby suppressing osteoclastogenesis; osteoclast-specific UCHL1 knockout mice develop severe osteoporosis. Osteoclast-specific conditional UCHL1 knockout mice; co-immunoprecipitation; in vitro ubiquitination/deubiquitination assay; K46 mutagenesis; NFATC1 nuclear transport assay; ovariectomy bone loss model International journal of biological sciences High 37215988
2022 UCHL1 binds, deubiquitinates, and stabilizes HIF-1α following myocardial infarction; UCHL1 knockout cardiomyocytes (via CRISPR/Cas9 in hiPSCs) show reduced HIF-1α expression and suppressed HIF-1α target genes; recombinant UCHL1 and AAV9-cardiac UCHL1 delivery protect against MI in mice. BioID proximity labeling + mass spectrometry; CRISPR/Cas9 UCHL1 knockout hiPSC-derived cardiomyocytes; Western blot for HIF-1α; HIF-1α target gene qRT-PCR; recombinant UCHL1 IP injection; AAV9-UCHL1 cardiac delivery; MI mouse model Redox biology Medium 35339825
2019 UCH-L1 regulates lung endothelial barrier function; UCHL1 knockdown or pharmacological inhibition (LDN-57444) decreases VE-cadherin and claudin-5 expression, reduces barrier enhancement by HGF, and increases thrombin-induced permeability; silencing FoxO1 transcription factor restores claudin-5 levels; UCHL1 inhibition in vivo increases ventilator-induced lung injury. UCHL1 siRNA; LDN-57444 inhibitor; transendothelial electrical resistance; VE-cadherin and claudin-5 Western blot; FoxO1 siRNA rescue; murine VILI model American journal of physiology. Lung cellular and molecular physiology Medium 33438509
2024 UCHL1 deficiency attenuates pulmonary arterial hypertension via reduction of AKT1; UCHL1 deubiquitinates AKT1 (specifically promotes K63-linked and reduces K48-linked ubiquitination), maintaining higher AKT1 levels; Uchl1 knockout rats and conditional Uchl1 knockout mice show reduced right ventricular hypertrophy, pressure, and vascular remodeling. UCHL1-silenced human pulmonary artery endothelial cells; Uchl1 knockout rats; conditional Uchl1 knockout mice (Tie2Cre); LDN57444 pharmacological inhibition; K63/K48-ubiquitinated Akt detection; right ventricular hemodynamics; vascular histology; three preclinical PAH models Circulation High 38695173
2023 UCHL1 binds, deubiquitinates, and stabilizes POM121 (a nuclear pore complex nucleoporin); stabilized POM121 regulates nuclear transport of E2F1 and c-MYC, maintaining neuroendocrine differentiation and promoting cancer progression in neuroendocrine carcinomas. Co-immunoprecipitation; deubiquitination assay; loss-of-function (siRNA/UCHL1 KO); nuclear fractionation for E2F1 and c-MYC; in vivo tumor growth and metastasis assays; UCHL1 inhibitor LDN-57444 Cell reports. Medicine Medium 38244540
2023 UCHL1 interacts with, deubiquitylates, and stabilizes ferredoxin reductase (FDXR), an important mitochondrial iron homeostasis protein; HCMV infection-induced loss of UCHL1 causes FDXR ubiquitination and degradation, leading to mitochondrial iron overload, AIM2 inflammasome activation, and vascular endothelial inflammatory injury. Co-immunoprecipitation; ubiquitination assay for FDXR; UCHL1 knockdown; HCMV infection model; mitochondrial iron measurement; AIM2 inflammasome activation assay; MCMV-infected mice Free radical biology & medicine Medium 38081437
2019 UCH-L1 promotes cross-presentation of antigens by dendritic cells by facilitating MHC class I molecule recycling; UCH-L1-deficient DCs have reduced ability to generate MHC I–peptide complexes and to cross-prime CD8 T cells in vivo; antigen uptake and phagosome maturation are unaffected, while intracellular MHC I colocalization with late endosomal/lysosomal compartments is reduced. UCH-L1-deficient mice; in vivo and in vitro CD8 T cell cross-priming assays; MHC I recycling assay; phagocytosis and phagosome maturation assays; MHC I colocalization imaging Journal of immunology Medium 31492742
2014 UCH-L1 activity increases podocyte hypertrophy and total protein content in membranous nephropathy; mechanistically, UCH-L1 increases cytoplasmic p27Kip1 by promoting its nuclear export and decreasing its poly-ubiquitination and proteasomal degradation; inhibition of UCH-L1 attenuates podocyte hypertrophy. UCH-L1 overexpression and knockdown in podocytes; UCH-L1 inhibitor; p27Kip1 nuclear/cytoplasmic fractionation; ubiquitination assay for p27Kip1; protein content measurement; human and rat MGN tissue analysis Biochimica et biophysica acta Medium 24583340
2016 UCH-L1 absence causes pure motor neuropathy with selective degeneration of motor (not sensory) axons; neuromuscular junctions are impaired in both slow- and fast-twitch muscle groups but spinal motor neuron cell bodies remain intact without signs of ER stress, indicating UCHL1 is specifically required for NMJ and motor axon maintenance rather than motor neuron survival. Uchl1(nm3419) UCHL1-/- mice; molecular and cellular marker expression analysis; electrophysiological recordings; NMJ morphological analysis; axon and sensory neuron histology Annals of clinical and translational neurology High 27231703
2021 UCHL1 promotes HGSOC (high-grade serous ovarian cancer) growth by maintaining protein homeostasis via the PSMA7-APEH-proteasome axis; UCHL1 silencing reduces PSMA7 and APEH expression and proteasome activity, causes polyubiquitinated protein accumulation, attenuates mTORC1 activity and protein synthesis, and induces terminal UPR. UCHL1 siRNA in HGSOC cells; in vivo xenograft metastasis model; transcriptional profiling; PSMA7 and APEH knockdown; proteasome activity assay; polyubiquitin accumulation; mTORC1 signaling assay Molecular cancer research : MCR Medium 33753553
2013 NF-κB transcription factor binds the UCH-L1 promoter at –300 bp and –109 bp sites and upregulates UCH-L1 expression; TNF-α and IL-1β cytokine stimulation of podocytes activates NF-κB and rapidly increases UCH-L1 mRNA and protein, while NF-κB inhibition (PDTC) prevents this upregulation. Electrophoretic mobility shift assay (EMSA); promoter reporter analysis; NF-κB inhibitor (PDTC); cytokine stimulation of podocytes; Western blot and qRT-PCR; immunohistochemistry of human lupus nephritis biopsies Cellular signalling Medium 23567262
2017 UCH-L1 promotes breast cancer cell invasion by interacting preferentially with Akt2 and activating Akt signaling; proximity-dependent BioID identified UCH-L1–Akt interaction, confirmed by pulldown with His-tagged recombinant UCH-L1 from cell lysate; UCH-L1 overexpression increases phosphorylated Akt while knockdown suppresses invasion. BioID proximity labeling; streptavidin pulldown; His-tagged recombinant UCH-L1 pulldown; phospho-Akt Western blot; invasion assays; UCH-L1 siRNA Journal of cellular biochemistry Medium 28636190
1996 PGP9.5/UCH-L1 was purified to homogeneity from bovine retina by ubiquitin-Sepharose affinity chromatography; the purified protein displays hydrolytic activity on ubiquitin ethyl ester (UbOEt) and reactivity with cysteine and histidine-specific reagents, confirming it is a cysteine/histidine-dependent ubiquitin C-terminal hydrolase with biochemical properties distinguishable from other UCH family members. Ubiquitin-Sepharose affinity chromatography; enzymatic assay with UbOEt; cysteine/histidine reagent inhibition; Km determination The Biochemical journal High 8809066

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. The Lancet. Neurology 462 30054151
2016 Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury. JAMA neurology 397 27018834
2006 Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell 369 16923396
2007 The functions of UCH-L1 and its relation to neurodegenerative diseases. Neurochemistry international 241 17586089
2016 Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction. The Biochemical journal 232 27515257
2009 UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein. Progress in neurobiology 214 19879917
2004 Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU international 153 15049988
2017 UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer. Journal of surgical oncology 110 28334432
2015 NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease. Human molecular genetics 107 25687137
2002 Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Oncogene 93 12082530
2020 The deubiquitinase UCHL1 regulates cardiac hypertrophy by stabilizing epidermal growth factor receptor. Science advances 92 32494592
2016 Assessment of Serum UCH-L1 and GFAP in Acute Stroke Patients. Scientific reports 92 27074724
2006 Silencing of the UCHL1 gene in human colorectal and ovarian cancers. International journal of cancer 90 16642472
2021 S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy. Neurosurgical review 89 34709508
2006 UCHL-1 is not a Parkinson's disease susceptibility gene. Annals of neurology 83 16450370
2001 Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Human molecular genetics 81 11555633
2023 Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury. Ageing research reviews 79 36681249
2016 Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia. Ageing research reviews 78 27702698
2008 Aberrant molecular properties shared by familial Parkinson's disease-associated mutant UCH-L1 and carbonyl-modified UCH-L1. Human molecular genetics 78 18250096
2017 Ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a therapeutic and diagnostic target in neurodegeneration, neurotrauma and neuro-injuries. Expert opinion on therapeutic targets 72 28434268
2019 Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America 70 30760601
2013 Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor. Molecular and cellular biology 68 23297343
2021 UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology. British journal of cancer 66 34497382
2019 High glucose-induced apoptosis and necroptosis in podocytes is regulated by UCHL1 via RIPK1/RIPK3 pathway. Experimental cell research 65 31247189
2006 PGP9.5 methylation in diffuse-type gastric cancer. Cancer research 65 16585221
2013 The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis. Cell communication and signaling : CCS 56 24090154
2009 Effects of UCH-L1 on alpha-synuclein over-expression mouse model of Parkinson's disease. Journal of neurochemistry 55 19141079
2008 The role of PGP9.5 as a tumor suppressor gene in human cancer. International journal of cancer 54 18512240
2020 Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients. Resuscitation 52 32445783
2021 Loss of UCHL1 rescues the defects related to Parkinson's disease by suppressing glycolysis. Science advances 51 34244144
2004 Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells. British journal of haematology 48 15491288
2003 PGP9.5 overexpression in esophageal squamous cell carcinoma. Hepato-gastroenterology 48 14571718
2020 The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase. Theranostics 46 32483437
2017 UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway. Journal of cellular biochemistry 46 28636190
1992 cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal hydrolase PGP9.5. Journal of biochemistry 44 1331034
2020 UCH-L1-mediated Down-regulation of Estrogen Receptor α Contributes to Insensitivity to Endocrine Therapy for Breast Cancer. Theranostics 43 32042339
2020 Deubiquitination of CD36 by UCHL1 promotes foam cell formation. Cell death & disease 42 32801299
2009 UCH-L1 expression of podocytes in diseased glomeruli and in vitro. The Journal of pathology 42 19214988
2022 UCHL1 Impairs Periodontal Ligament Stem Cell Osteogenesis in Periodontitis. Journal of dental research 40 36112902
2016 Are UCH-L1 and GFAP promising biomarkers for children with mild traumatic brain injury? Brain injury 40 27416022
2024 The game changer: UCH-L1 and GFAP-based blood test as the first marketed in vitro diagnostic test for mild traumatic brain injury. Expert review of molecular diagnostics 39 38275158
2008 PGP9.5 methylation as a marker for metastatic colorectal cancer. Anticancer research 39 19035297
2024 Diagnostic Performance of GFAP, UCH-L1, and MAP-2 Within 30 and 60 Minutes of Traumatic Brain Injury. JAMA network open 38 39230905
2022 UCHL1 protects against ischemic heart injury via activating HIF-1α signal pathway. Redox biology 36 35339825
2018 UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice. Blood 36 30257881
2016 Absence of UCHL 1 function leads to selective motor neuropathy. Annals of clinical and translational neurology 35 27231703
2016 Wnt/β-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy. International journal of molecular sciences 35 27571062
2013 Association of promoter methylation of VGF and PGP9.5 with ovarian cancer progression. PloS one 35 24086249
2004 Genetic causes of Parkinson's disease: UCHL-1. Cell and tissue research 34 15221445
2022 Structural basis for specific inhibition of the deubiquitinase UCHL1. Nature communications 32 36216817
2017 The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis. Brain injury 32 29087740
2001 Ubiquitin C-terminal hydrolase-L1 (PGP9.5) expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines, neurotrophic factors or heat stress. Neuropathology and applied neurobiology 32 11437990
2024 UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas. Cell reports. Medicine 31 38244540
2006 Substrate recognition and catalysis by UCH-L1. Biochemistry 31 17144664
1991 Reduction in the number of UCHL-1+ cells and IL-2 production in the peripheral blood of patients with visceral leishmaniasis. Journal of immunology (Baltimore, Md. : 1950) 31 1824848
1997 Low specificity of PGP9.5 expression for detection of micrometastatic neuroblastoma. British journal of cancer 30 9192981
2025 Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop. Cell death and differentiation 28 40016338
2017 Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders. Current protein & peptide science 27 26899237
2021 Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7-APEH-Proteasome Axis in High-grade Serous Ovarian Carcinoma. Molecular cancer research : MCR 26 33753553
2016 UCH-L1 Inhibition Decreases the Microtubule-Binding Function of Tau Protein. Journal of Alzheimer's disease : JAD 26 26444754
2024 Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1β production in human macrophages and microglia. Cell reports 25 38669140
2021 The Epstein-Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth. Proceedings of the National Academy of Sciences of the United States of America 25 34686609
2017 Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 28500221
2013 The regulation of the UCH-L1 gene by transcription factor NF-κB in podocytes. Cellular signalling 25 23567262
2002 Expression of PGP9.5 in ductal cells of the rat pancreas during development and regeneration: can it be a marker for pancreatic progenitor cells? Endocrine journal 24 12008752
2024 A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression. Nature communications 23 39389988
2014 N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage. PloS one 23 24959670
2019 UCH-L1 is a Poor Serum Biomarker of Murine Traumatic Brain Injury After Polytrauma. The Journal of surgical research 22 31279265
2022 UCHL1 Promoted Polarization of M1 Macrophages by Regulating the PI3K/AKT Signaling Pathway. Journal of inflammation research 21 35153498
2019 UCHL1 regulates muscle fibers and mTORC1 activity in skeletal muscle. Life sciences 21 31356902
1993 Differentiation of reactive from neoplastic small-cell lymphoid aggregates in paraffin-embedded marrow particle preparations using L-26 (CD20) and UCHL-1 (CD45RO) monoclonal antibodies. American journal of clinical pathology 21 7679873
2024 Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension. Circulation 20 38695173
2021 UCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivo. American journal of physiology. Lung cellular and molecular physiology 20 33438509
2021 UCHL1 regulates inflammation via MAPK and NF-κB pathways in LPS-activated macrophages. Cell biology international 20 34288216
2020 UCHL1 regulates oxidative activity in skeletal muscle. PloS one 20 33137160
2017 UCH-L1 Inhibition Suppresses tau Aggresome Formation during Proteasomal Impairment. Molecular neurobiology 20 28540657
2013 Cardiac sympathetic innervation and PGP9.5 expression by cardiomyocytes after myocardial infarction: effects of central MR blockade. American journal of physiology. Heart and circulatory physiology 20 24124186
1990 Detection of B- and T-cells in paraffin-embedded tissue sections. Diagnostic utility of commercially obtained 4KB5 and UCHL-1. American journal of clinical pathology 20 2403743
2023 The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling. International journal of biological sciences 19 37215988
2019 UCHL1 loss alters the cell-cycle in metastatic pancreatic neuroendocrine tumors. Endocrine-related cancer 19 30689542
2016 α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats. Inflammopharmacology 19 27671329
2010 Silencing of the UCHL1 gene in giant cell tumors of bone. International journal of cancer 19 20104524
1996 Affinity purification and characterization of protein gene product 9.5 (PGP9.5) from retina. The Biochemical journal 19 8809066
2024 An automated blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) to predict the absence of intracranial lesions on head CT in adult patients with mild traumatic brain injury: BRAINI, a multicentre observational study in Europe. EBioMedicine 18 39612652
2023 UCHL1 facilitates protein aggregates clearance to enhance neural stem cell activation in spinal cord injury. Cell death & disease 18 37507386
2021 UCH-L1 and UCH-L3 regulate the cancer stem cell-like properties through PI3 K/Akt signaling pathway in prostate cancer cells. Animal cells and systems 18 34745437
2020 Abolishing UCHL1's hydrolase activity exacerbates TBI-induced axonal injury and neuronal death in mice. Experimental neurology 18 33159930
2012 UCHL1 regulates ubiquitination and recycling of the neural cell adhesion molecule NCAM. The FEBS journal 18 23061666
2000 Expression of PGP9.5 on Langerhans' cells and their precursors. Acta dermato-venereologica 18 10721824
2024 Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17. Cellular and molecular life sciences : CMLS 17 38478109
2022 Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy. Pediatric research 17 35273370
2017 Decreased Expression of α-Synuclein, Nogo-A and UCH-L1 in Patients with Schizophrenia: A Preliminary Serum Study. Psychiatry investigation 17 28539953
2023 UCHL1 aggravates skin fibrosis through an IGF-1-induced Akt/mTOR/HIF-1α pathway in keloid. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 37256780
2023 UCHL1 deficiency upon HCMV infection induces vascular endothelial inflammatory injury mediated by mitochondrial iron overload. Free radical biology & medicine 16 38081437
2022 Ubiquitin C-terminal hydrolase L1 (UCHL1), a double-edged sword in mammalian oocyte maturation and spermatogenesis. Cell proliferation 16 36218038
2022 UCHL1 promotes cancer stemness in triple-negative breast cancer. Pathology, research and practice 16 36434856
2019 Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules. Journal of immunology (Baltimore, Md. : 1950) 16 31492742
2020 Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway. International journal of molecular sciences 15 32516975
2020 BDNF and IL-8, But Not UCHL-1 and IL-11, Are Markers of Brain Injury in Children Caused by Mild Head Trauma. Brain sciences 15 32987792
2014 UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation. Biochimica et biophysica acta 15 24583340

Missed literature

Know a paper Affinage missed for UCHL1? Flag it for the maintainers and the community.

No submissions yet.