Affinage

USP37

Ubiquitin carboxyl-terminal hydrolase 37 · UniProt Q86T82

Length
979 aa
Mass
110.2 kDa
Annotated
2026-04-28
46 papers in source corpus 31 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP37 is a ubiquitin-specific protease whose catalytic activity is cell-cycle regulated by phosphorylation and whose broad substrate repertoire connects it to DNA replication, DNA damage repair, chromosome cohesion, and signal transduction. CDK2-mediated phosphorylation activates USP37 in S phase, while sequential targeting by SCF(βTrCP)/Plk1 at G2/M and APC(CDH1) in G1 ensures its periodic destruction; within S phase, USP37 binds CDC45 on the CMG helicase and deubiquitinates MCM7, counteracting CUL2(LRR1)- and TRAIP-mediated ubiquitylation to prevent unscheduled replisome disassembly, and it stabilizes CHK1 and RPA at stalled forks to maintain the replication checkpoint and protect forks from MRE11-dependent degradation (PMID:21596315, PMID:23027877, PMID:40379725, PMID:34509474, PMID:40548939). At DNA double-strand breaks, USP37 removes RNF168-induced ubiquitin conjugates to limit RAP80-BRCA1 spreading and promote PALB2-dependent homologous recombination, an activity enhanced by ATM-dependent phosphorylation that also stimulates BLM helicase stabilization (PMID:26101254, PMID:34606619). Beyond genome maintenance, USP37 deubiquitinates and stabilizes diverse substrates—including cyclin A, c-Myc, HIF2α, SNAI1, p27, WAPL, FOXO4, and β-catenin—linking it to cell-cycle progression, epithelial–mesenchymal transition, stemness, and senescence maintenance, with UIM2 and UIM3 providing proximal ubiquitin recognition that enhances catalytic rate (PMID:24324262, PMID:30858488, PMID:22665064, PMID:25284584, PMID:32461361, PMID:31911859, PMID:41980094).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2011 High

    Establishing USP37 as a cell-cycle-regulated deubiquitinase that antagonizes APC(CDH1) revealed how G1/S entry is fine-tuned: USP37 removes K11-linked ubiquitin from cyclin A, is itself an APC(CDH1) substrate, and requires CDK2 phosphorylation for full activity.

    Evidence Co-IP, in vivo ubiquitination, cell cycle synchronization, mass spectrometry in human cells

    PMID:21596315

    Open questions at the time
    • Precise CDK2 phosphosites were not fully resolved
    • In vitro reconstitution of K11-chain cleavage not shown
    • Whether USP37 acts on other APC substrates beyond cyclin A was unknown
  2. 2012 High

    Demonstrating that Plk1-dependent phosphorylation targets USP37 to SCF(βTrCP) for degradation at G2/M established the second layer of periodic USP37 destruction and explained why USP37 activity is confined to S phase.

    Evidence Phosphosite mutagenesis, Co-IP with βTrCP, Plk1 chemical/genetic manipulation, flow cytometry

    PMID:23027877

    Open questions at the time
    • The precise phosphodegron sequence and in vitro reconstitution of SCF(βTrCP) ubiquitylation of USP37 were not fully detailed
    • Interplay between APC(CDH1) and SCF(βTrCP) destruction pathways was not quantitatively resolved
  3. 2012 High

    Identification of p27 and PLZF/RARA as USP37 substrates expanded its role beyond cyclin A to tumor suppressor stabilization and oncoprotein maintenance, and the finding that REST represses USP37 transcription placed USP37 under epigenetic control in medulloblastoma.

    Evidence Co-IP, catalytic mutant rescue, domain mapping, hematopoietic progenitor transformation assay

    PMID:22665064 PMID:23208507

    Open questions at the time
    • Whether REST-mediated USP37 repression occurs in tissues beyond medulloblastoma was untested
    • Direct structural basis for PLZF/RARA recognition unknown
  4. 2013 High

    Systematic mutagenesis of the three UIMs established that UIM2 and UIM3 (not UIM1) are required for ubiquitin-chain binding and full isopeptidase activity, defining the proximal ubiquitin recognition mechanism.

    Evidence In vitro ubiquitin chain binding and isopeptidase assays with UIM point mutants

    PMID:24324262

    Open questions at the time
    • Structural basis for UIM2/3 selectivity unresolved
    • Whether UIMs confer any chain-type preference in vivo was unclear
  5. 2014 High

    Identification of c-Myc as a USP37 substrate connected USP37 to oncogene stabilization in lung cancer, broadening its substrate repertoire to transcription factors controlling proliferation.

    Evidence DUB screen, Co-IP, ubiquitination assay, cycloheximide chase in lung cancer cells

    PMID:25284584

    Open questions at the time
    • Whether USP37 opposes a specific E3 ligase for c-Myc was not defined
    • In vivo tumor model validation not provided in this study
  6. 2015 High

    Demonstrating that USP37 removes RNF168-induced ubiquitin at DSBs and limits RAP80-BRCA1 spreading established USP37 as a regulator of homologous recombination pathway choice.

    Evidence Genetic epistasis with RAP80 double depletion, HR reporter assay, DSB immunofluorescence

    PMID:26101254

    Open questions at the time
    • Direct biochemical cleavage of RNF168 products not reconstituted in vitro
    • Whether USP37 acts at all DSBs or is context-dependent was unknown
  7. 2015 High

    Discovery that USP37 deubiquitinates WAPL to maintain sister chromatid cohesion revealed a mitotic function distinct from its S-phase roles, supported by catalytic mutant rescue and UIM2/3 dependence.

    Evidence In vitro deubiquitylation of WAPL immunoprecipitates, C350A catalytic mutant rescue, UIM mutagenesis, cohesion/alignment phenotypes

    PMID:26299517

    Open questions at the time
    • The E3 ligase ubiquitylating WAPL was not identified
    • How USP37 activity persists in mitosis given its G2/M degradation was not fully reconciled
  8. 2016 High

    Identification of Cdt1 as a USP37 substrate and evidence that USP37 promotes MCM chromatin loading linked USP37 directly to replication origin licensing.

    Evidence Co-IP, ubiquitination assay, chromatin fractionation, DNA fiber assay

    PMID:27296872

    Open questions at the time
    • Whether USP37 opposes CRL4-Cdt2 or SCF-Skp2 for Cdt1 regulation was not resolved
    • Risk of re-replication from Cdt1 over-stabilization not quantified
  9. 2019 High

    Kinetic reconstitution showed UIM3 recognizes the proximal ubiquitin of K48-linked di-ubiquitin to increase kcat, providing the first quantitative enzymological framework for USP37 catalysis, validated by engineered ubiquitin variant inhibitors.

    Evidence In vitro enzymatic kinetics with defined di-Ub substrates, UIM mutagenesis, UbV inhibitor biochemistry

    PMID:30858488

    Open questions at the time
    • Crystal structure of USP37 catalytic domain with ubiquitin not available
    • Kinetics with longer polyubiquitin chains not characterized
  10. 2019 High

    Demonstration that USP37 stabilizes SNAI1 through catalytic-activity-dependent deubiquitination connected USP37 to epithelial–mesenchymal transition and cell migration.

    Evidence Co-IP, catalytic mutant (C350S), SNAI1 rescue of migration phenotype

    PMID:31911859 PMID:33391500

    Open questions at the time
    • Whether GSK-3β phosphorylation of SNAI1 is universally required for USP37 recognition across cell types was not tested
  11. 2020 High

    Identification of HIF2α as a USP37 substrate in ccRCC established USP37 as a driver of the VHL-independent HIF2α stabilization axis in kidney cancer.

    Evidence DUB cDNA library screen, Co-IP, ubiquitination assay, orthotopic xenograft

    PMID:32461361

    Open questions at the time
    • Whether USP37 opposes VHL-mediated or VHL-independent ubiquitylation of HIF2α not fully dissected
    • Structural basis for HIF2α recognition unknown
  12. 2021 High

    Showing that ATM phosphorylates USP37 to enhance BLM binding and stabilization established a phospho-switch that links DNA damage signaling to helicase protection during the repair response.

    Evidence Co-IP, ATM kinase assay, phosphorylation validation, BLM ubiquitination/proteolysis measurement, in vivo mouse model

    PMID:34606619

    Open questions at the time
    • Precise ATM phosphosite on USP37 and its structural consequences not fully defined
    • Whether USP37-BLM interaction occurs at stalled forks vs. DSBs not distinguished
  13. 2021 High

    Discovery that USP37 deubiquitinates CHK1 to maintain the replication checkpoint revealed that USP37 protects genome integrity at two levels: stabilizing a checkpoint kinase and maintaining fork progression.

    Evidence Co-IP, ubiquitination assay, replication stress markers (γH2AX, 53BP1), thymidine analog labeling

    PMID:34509474

    Open questions at the time
    • The E3 ligase opposed by USP37 for CHK1 ubiquitylation not identified
    • Whether CHK1 stabilization and CMG protection are coordinated or independent functions not resolved
  14. 2025 High

    Convergent work from multiple laboratories established that USP37 binds CDC45 on the CMG helicase and deubiquitinates MCM7, directly counteracting CUL2(LRR1)- and TRAIP-mediated replisome ubiquitylation to prevent premature fork disassembly during S phase — defining USP37's most specific replication function.

    Evidence Proteomics, Xenopus egg extract reconstitution, AlphaFold-guided mutagenesis displacing USP37 from CDC45, genetic epistasis (CUL2/LRR1 and TRAIP double depletions), chromatin fractionation

    PMID:40379725 PMID:40411782 PMID:40533495

    Open questions at the time
    • Full atomic structure of USP37-CDC45 interface not experimentally determined
    • Whether USP37 distinguishes fork termination signals from stalling signals is unresolved
    • Quantitative contribution of USP37 vs. other DUBs to CMG protection in different organisms unknown
  15. 2025 High

    Discovery that USP37 deubiquitinates RPA at stalled forks and limits HLTF-dependent fork remodeling to prevent MRE11-mediated degradation revealed a fork protection mechanism that explains PARP inhibitor resistance in BRCA1-deficient cancers.

    Evidence Genome-wide CRISPR screen, Co-IP, DNA fiber assay, HLTF epistasis, cell viability in BRCA1-deficient cells

    PMID:40548939

    Open questions at the time
    • Whether RPA deubiquitination and MCM7 deubiquitination are coordinated at the same fork not established
    • Structural basis for RPA recognition by USP37 unknown
  16. 2025 High

    CHK2-mediated phosphorylation of USP37 at Thr589 during persistent DNA damage enhances FOXO4 binding and K48-chain removal, establishing a senescence maintenance axis where USP37 stabilizes FOXO4 to resist apoptosis.

    Evidence DUB screen, Co-IP, CHK2 kinase assay, Thr589 phospho-mapping, FOXO4 rescue of apoptosis phenotype

    PMID:41980094

    Open questions at the time
    • Whether the CHK2-USP37-FOXO4 axis operates in therapy-induced senescence not tested
    • Interplay with ATM-dependent phosphorylation events on USP37 not integrated
  17. 2025 High

    CDK1 phosphorylation of USP37 at Thr631 enhances its activity toward SND1, adding another CDK-dependent phospho-activation mode and a new oncogenic substrate in colorectal cancer.

    Evidence Multi-omics (proteomics, ubiquitinomics, interactomics), in vitro CDK1 kinase assay, Co-IP, virtual drug screening

    PMID:40486858

    Open questions at the time
    • Whether CDK1-Thr631 and CDK2-mediated phosphorylation are additive or context-dependent unknown
    • In vivo validation in patient-derived models not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution experimental structure of USP37 (catalytic domain with UIMs and ubiquitin) exists, and the integrative logic by which USP37 selects among its many substrates at distinct cell-cycle stages and DNA damage contexts remains unresolved.
  • Atomic-resolution structure of full-length USP37 needed
  • Quantitative substrate-selectivity model incorporating phosphorylation, UIM engagement, and subcellular localization lacking
  • Whether loss-of-function USP37 mutations cause a human Mendelian disorder is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 17 GO:0016787 hydrolase activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-69306 DNA Replication 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 2
Partners
BLMCDC45CDH1CHEK1FOXO4MCM7SNAI1WAPL

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 USP37 binds CDH1 and removes degradative K11-linked polyubiquitin from cyclin A, thereby antagonizing APC(CDH1)-mediated degradation. USP37 expression is induced by E2F transcription factors in G1, peaks at G1/S, and is itself degraded in late mitosis as a substrate of APC(CDH1). Phosphorylation of USP37 by CDK2 stimulates its full deubiquitinase activity; in mitosis, CDK2 no longer phosphorylates USP37, abolishing this activity. Co-immunoprecipitation, in vivo ubiquitination assay, cell cycle synchronization, overexpression/knockdown with flow cytometry, mass spectrometry Molecular cell High 21596315
2012 USP37 is targeted for degradation at the G2/M transition by the SCF(βTrCP) ubiquitin ligase. This interaction requires Polo-like kinase 1 (Plk1)-dependent phosphorylation of USP37; mutation of the phospho-sites abolishes βTrCP binding and renders USP37 resistant to degradation. Expression of this stabilized mutant hinders the G2/M transition. Co-immunoprecipitation, cell synchronization, chemical/genetic manipulation of Plk1, phosphosite mutagenesis, flow cytometry The Journal of biological chemistry High 23027877
2012 USP37 directly binds and deubiquitinates p27 (CDKN1B), stabilizing it and blocking cell proliferation. This activity requires the conserved catalytic cysteine; a catalytic mutant fails to rescue p27 stabilization. USP37 expression is transcriptionally repressed by REST in medulloblastoma cells. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (catalytic cysteine), knockdown/overexpression with proliferation readouts Oncogene High 22665064
2012 USP37 interacts with the oncogenic fusion protein PLZF/RARA through the PLZF moiety via its N-terminal domain, deubiquitinates PLZF/RARA, and sustains its steady-state levels; depletion of USP37 reduces PLZF/RARA half-life and alleviates PLZF/RARA-mediated cell transformation. RNAi screen, co-immunoprecipitation, domain mapping, ubiquitination/half-life assay, primary mouse hematopoietic progenitor cell transformation assay Oncogene High 23208507
2013 USP37 contains three ubiquitin-interacting motifs (UIMs); UIM2 and UIM3 (but not UIM1) are required for binding ubiquitinated proteins and both K48- and K63-linked ubiquitin chains in vitro and in cells. Mutations in UIM2 or UIM3 reduce USP37 isopeptidase activity without altering its nuclear localization, indicating UIMs confer full catalytic activity but not ubiquitin chain substrate specificity. UIM mutagenesis, in vitro ubiquitin chain binding assay, isopeptidase activity assay, cellular ubiquitinated protein binding assay The Journal of biological chemistry High 24324262
2014 USP37 directly binds and deubiquitinates c-Myc in a DUB activity-dependent manner, preventing its proteasomal degradation and stabilizing c-Myc protein levels in lung cancer cells. USP screen, co-immunoprecipitation, in vivo ubiquitination assay, overexpression/knockdown with cycloheximide chase Oncogene High 25284584
2014 HBx oncoprotein of hepatitis B virus directly interacts with USP37 and promotes its translocation from the nucleus to the cytoplasm, preventing USP37 ubiquitination by APC/CDH1 and SCF/βTrCP, thereby stabilizing USP37 and cyclin A to deregulate cell cycle progression. Co-immunoprecipitation, confocal microscopy, flow cytometry, western blot PloS one Medium 25347529
2015 USP37 and USP26 are recruited to DNA double-strand breaks where they remove RNF168-induced ubiquitin conjugates. Depletion of USP37 disrupts homologous recombination (HR), an effect rescued by simultaneous depletion of RAP80. USP37 limits excessive spreading of RAP80-BRCA1 from DSBs and promotes BRCA1 association with PALB2. Genetic screen, RNAi, immunofluorescence at DSBs, epistasis analysis (double depletion), HR reporter assay Nucleic acids research High 26101254
2015 USP37 associates with the cohesin complex and with WAPL (via UIM2 and UIM3). Depletion of USP37 reduces chromatin-associated WAPL stability and increases WAPL ubiquitylation in mitosis. Purified wild-type USP37, but not catalytically impaired USP37(C350A), deubiquitylates WAPL immunoprecipitates in vitro. USP37 depletion causes cohesion defects, centrosome integrity problems, and chromosome alignment defects rescued by RNAi-resistant WT USP37 but not C350A. RNAi screen, co-immunoprecipitation, in vitro deubiquitylation assay, UIM mutagenesis, catalytic mutant rescue, flow cytometry, immunofluorescence Current biology : CB High 26299517
2015 USP37 directly interacts with 14-3-3γ and stabilizes it through its catalytic deubiquitinase activity, preventing 14-3-3γ degradation. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown Oncotarget Medium 26427597
2016 USP37 is the first identified deubiquitinase for Cdt1. USP37 interacts with and deubiquitinates Cdt1 in vivo, stabilizing a phosphorylated form of Cdt1, particularly in G1 and G1/S phases. USP37 overexpression promotes MCM loading onto chromatin; USP37 knockdown reduces replication fork speed. Overexpression screen, co-immunoprecipitation, in vivo ubiquitination assay, chromatin fractionation, DNA fiber assay Molecular oncology High 27296872
2017 REST-associated G9a histone methyltransferase promotes H3K9 mono-, di-, and trimethylation at the USP37 promoter to repress USP37 gene expression in medulloblastoma cells, defining a REST/G9a/H3K9me-USP37 epigenetic regulatory axis. ChIP assay, pharmacological and genetic inhibition of G9a, isogenic REST cell lines, in vivo tumor model Molecular cancer research : MCR High 28483947
2018 USP37 interacts with and stabilizes Gli-1 (a Hedgehog pathway effector) via deubiquitination in breast cancer stem cells, and this promotes stemness, EMT, and cell invasion. Co-immunoprecipitation, CHX chase, immunofluorescence, knockdown/overexpression, in vivo xenograft Journal of experimental & clinical cancer research : CR Medium 30482232
2019 USP37 directly binds, deubiquitinates, and stabilizes SNAI1 (Snail1), preventing its proteasomal degradation. Overexpression of wild-type USP37, but not catalytically inactive C350S mutant, promotes cancer cell migration. USP37 depletion suppresses SNAI1 protein levels and cell migration, reversible by SNAI1 re-expression. Co-immunoprecipitation, in vivo ubiquitination assay, catalytic mutant (C350S), rescue experiments, migration assay American journal of cancer research High 31911859
2019 The third UIM of USP37 recognizes the proximal ubiquitin moiety of K48-linked di-ubiquitin to potentiate cleavage activity, primarily by increasing the catalytic rate (kcat). Three ubiquitin variant (UbV) inhibitors were developed that selectively engage distinct binding sites in USP37 (including the three UIMs), validating their functional roles in catalysis. In vitro enzymatic kinetics with di-Ub substrates, UIM mutagenesis, UbV inhibitor design and biochemical characterization Scientific reports High 30858488
2020 USP37 directly binds HIF2α and promotes its deubiquitination in an enzymatically dependent manner, stabilizing HIF2α protein in clear cell renal cell carcinoma (ccRCC). USP37 depletion leads to HIF2α downregulation and decreased ccRCC proliferation and tumorigenesis. DUB cDNA library binding screen, co-immunoprecipitation, ubiquitination assay, MTS proliferation assay, colony formation, orthotopic xenograft Proceedings of the National Academy of Sciences of the United States of America High 32461361
2020 USP37 deubiquitinates Snail and co-localizes with Snail in the nucleus in lung cancer cells. USP37 overexpression promotes lung cancer cell migration, and Snail depletion abolishes this effect. Co-immunoprecipitation, ubiquitination assay, immunofluorescence co-localization, knockdown/overexpression, migration assay Frontiers in genetics Medium 31998374
2021 USP37 interacts with and deubiquitinates BLM helicase, stabilizing it. DNA double-strand breaks promote ATM-dependent phosphorylation of USP37, which enhances USP37-BLM binding. USP37 knockdown increases BLM polyubiquitination, accelerates its proteolysis, and impairs DNA damage response, sensitizing breast cancer cells to DNA-damaging agents. Co-immunoprecipitation, ubiquitination assay, ATM kinase assay, phosphorylation validation, knockdown/overexpression, cell viability, in vivo mouse model Nucleic acids research High 34606619
2021 USP37 interacts with and deubiquitinates Snail1 (SNAI1); GSK-3β-dependent phosphorylation of Snail1 is essential for USP37-mediated Snail1 deubiquitination. PLAGL2 transcriptionally activates USP37, which then promotes Snail1-mediated gastric cancer cell proliferation and migration. Co-immunoprecipitation, ubiquitination assay, luciferase reporter for transcription, phosphorylation experiments, knockdown/overexpression, in vivo xenograft Theranostics High 33391500
2021 USP37 deubiquitinates checkpoint kinase 1 (CHK1), promoting its stability. USP37-depleted cells exhibit reduced CHK1 levels, attenuated replication checkpoint function, increased replication stress markers (γH2AX, 53BP1), and hypersensitivity to replication stress agents. Flow cytometry, thymidine analog labeling, co-immunoprecipitation, ubiquitination assay, knockdown with replication stress readouts The Journal of biological chemistry High 34509474
2022 USP37 deubiquitinates CDC73/parafibromin via K48-specific ubiquitin chain removal, stabilizing it. Interaction requires the β-catenin binding site of CDC73 and UIM2/3 of USP37. CDC73 and USP37 co-localize in the nucleus. Catalytically inactive USP37(C350S) fails to deubiquitinate CDC73. Yeast two-hybrid, co-immunoprecipitation, domain mapping, ubiquitination assay, catalytic mutant (C350S), co-localization imaging International journal of molecular sciences Medium 35742816
2023 USP37 directly interacts with estrogen receptor alpha (ERα), stabilizes it by inhibiting K48-specific polyubiquitination in a deubiquitinase activity-dependent manner, and promotes ERα target gene expression and breast cancer cell proliferation. Co-immunoprecipitation, ubiquitination assay, cycloheximide chase, knockdown with ERα rescue, ERE luciferase reporter Cancer science Medium 36221793
2023 USP37 stabilizes β-catenin by inhibiting its ubiquitination, thereby promoting Wnt/β-catenin signaling, angiogenesis, and metastasis in colorectal cancer. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vivo xenograft, HUVEC angiogenesis assay American journal of cancer research Medium 37424824
2024 USP37 deubiquitinates SAMHD1 by directly recognizing it (not by targeting the E3 ligase), removing its ubiquitin chains and reversing Vpx-mediated degradation of SAMHD1. The deubiquitinase activity of USP37 and its UIMs are required; phosphorylation state of USP37 does not affect this activity. USP37 stabilizes SAMHD1 to enhance suppression of LINE-1 retrotransposition. Co-immunoprecipitation, ubiquitination assay, catalytic mutant analysis, UIM mutant analysis, retrotransposition reporter assay Journal of virology Medium 39655951
2025 USP37 binds the CMG helicase (CDC45-MCM2-7-GINS) via CDC45, and deubiquitinates MCM7 to prevent unscheduled replisome disassembly during S phase. USP37 counteracts ubiquitylation of CMG by CUL2(LRR1), which normally drives replisome disassembly at termination. Depletion of CUL2(LRR1) suppresses sensitivity of USP37 mutants to DNA synthesis defects. USP37 also counteracts TRAIP ubiquitin ligase; TRAIP loss specifically suppresses USP37 mutant sensitivity to topological stress. Structure-guided mutations displacing USP37 from CDC45 phenocopy loss of catalytic activity. Proteomics/interactomics, biochemical ubiquitination assay, targeted loss-of-function screen, single-cell quantitative analysis, Xenopus egg extract reconstitution, AlphaFold-guided structural modeling with mutagenesis, genetic epistasis (double mutant/depletion), chromatin fractionation Nature communications / Cell reports / Nucleic acids research High 40379725 40411782 40533495
2025 CDK1 phosphorylates USP37 at threonine 631, enhancing its deubiquitinase activity and consequently stabilizing SND1 protein to drive colorectal cancer malignancy. USP37 was identified as the deubiquitinase of SND1 through proteomics, ubiquitinomics, and interactomics approaches. Proteomics, ubiquitinomics, interactomics, phosphorylation site mapping, co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, virtual screening for inhibitor Dacarbazine Acta pharmaceutica Sinica. B High 40486858
2025 USP37 interacts with and deubiquitinates RPA at stalled replication forks, limiting excessive RPA accumulation. USP37 also limits HLTF accumulation at replication forks and prevents MRE11-dependent fork degradation; depletion of HLTF reverses replication-associated damage in USP37 knockout cells. This fork protection promotes survival of BRCA1-deficient cells and contributes to PARP inhibitor resistance. Genome-wide CRISPR screen, co-immunoprecipitation, ubiquitination assay, DNA fiber assay, knockdown epistasis (HLTF depletion), cell viability assay Nucleic acids research High 40548939
2025 CHK2 phosphorylates USP37 at Thr589 during persistent DNA damage response in senescent cells, enhancing USP37 binding to FOXO4. USP37 directly interacts with FOXO4 and removes K48-linked polyubiquitin chains to stabilize it. USP37 depletion destabilizes FOXO4 and sensitizes senescent cells to apoptosis, an effect rescued by FOXO4 re-expression. Deubiquitinase screen, co-immunoprecipitation, in vivo ubiquitination assay, phosphorylation mapping, CHK2 kinase assay, knockdown/overexpression with apoptosis readout, rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 41980094
2025 USP37 deubiquitinates and stabilizes Raptor (a component of mTORC1) and GLI1 (Hedgehog pathway effector) in medulloblastoma cells. Under low USP37, reduced Raptor stability and mTORC1 activity decrease 4EBP1 phosphorylation and increase its interaction with eIF4E, inhibiting CAP-dependent translation. USP37-mediated GLI1 stabilization increases SHH pathway activity and CCND1 expression. Co-immunoprecipitation, ubiquitination assay, biochemical pathway analysis, genetic knockdown/overexpression Oncogene Medium 41408466

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Molecular cell 134 21596315
2014 USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer. Oncogene 133 25284584
2018 Abnormally elevated USP37 expression in breast cancer stem cells regulates stemness, epithelial-mesenchymal transition and cisplatin sensitivity. Journal of experimental & clinical cancer research : CR 85 30482232
2015 The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. Nucleic acids research 64 26101254
2021 PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1. Theranostics 61 33391500
2020 USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination. Frontiers in genetics 52 31998374
2020 USP37 promotes deubiquitination of HIF2α in kidney cancer. Proceedings of the National Academy of Sciences of the United States of America 46 32461361
2012 Skp1-Cul1-F-box ubiquitin ligase (SCF(βTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry. The Journal of biological chemistry 41 23027877
2012 The deubiquitylase USP37 links REST to the control of p27 stability and cell proliferation. Oncogene 39 22665064
2012 The deubiquitinating enzyme USP37 regulates the oncogenic fusion protein PLZF/RARA stability. Oncogene 38 23208507
2016 USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Molecular oncology 37 27296872
2015 The Deubiquitinase USP37 Regulates Chromosome Cohesion and Mitotic Progression. Current biology : CB 35 26299517
2021 USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. Nucleic acids research 32 34606619
2017 Regulation of USP37 Expression by REST-Associated G9a-Dependent Histone Methylation. Molecular cancer research : MCR 32 28483947
2015 Deubiquitinating enzyme USP37 regulating oncogenic function of 14-3-3γ. Oncotarget 26 26427597
2013 Ubiquitin-interacting motifs confer full catalytic activity, but not ubiquitin chain substrate specificity, to deubiquitinating enzyme USP37. The Journal of biological chemistry 26 24324262
2014 The HBx oncoprotein of hepatitis B virus deregulates the cell cycle by promoting the intracellular accumulation and re-compartmentalization of the cellular deubiquitinase USP37. PloS one 23 25347529
2021 Intermittent hypoxia-induced downregulation of microRNA-320b promotes lung cancer tumorigenesis by increasing CDT1 via USP37. Molecular therapy. Nucleic acids 19 33898105
2019 USP37 is a SNAI1 deubiquitinase. American journal of cancer research 16 31911859
2019 The ubiquitin interacting motifs of USP37 act on the proximal Ub of a di-Ub chain to enhance catalytic efficiency. Scientific reports 14 30858488
2022 Topoisomerase IIA in adult NSCs regulates SVZ neurogenesis by transcriptional activation of Usp37. Nucleic acids research 13 36029179
2021 miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37. Cancer research and treatment 13 34352998
2021 The deubiquitinating enzyme USP37 enhances CHK1 activity to promote the cellular response to replication stress. The Journal of biological chemistry 12 34509474
2021 USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin. International journal of medical sciences 9 33390801
2023 Stabilization of estrogen receptor α by USP37 contributes to the progression of breast cancer. Cancer science 8 36221793
2023 USP37 promotes angiogenesis and metastasis in colorectal cancer by facilitating β-catenin stability. American journal of cancer research 6 37424824
2022 USP37 Deubiquitinates CDC73 in HPT-JT Syndrome. International journal of molecular sciences 5 35742816
2022 The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c-Myc expression. International wound journal 5 36333840
2025 USP37 protects mammalian cells during DNA replication stress by counteracting CUL2LRR1 and TRAIP. Cell reports 4 40411782
2025 CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer. Acta pharmaceutica Sinica. B 4 40486858
2025 USP37-stabilized SALL4 promotes the keloid formation by PI3K/AKT pathway. Scientific reports 3 40038378
2025 USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination. Nature communications 3 40379725
2024 USP37 prevents premature disassembly of stressed replisomes by TRAIP. bioRxiv : the preprint server for biology 3 39282314
2024 Deubiquitinase USP37 enhances the anti-HIV-2/SIV ability of the host restriction factor SAMHD1. Journal of virology 3 39655951
2023 Investigating In Situ Expression of c-MYC and Candidate Ubiquitin-Specific Proteases in DLBCL and Assessment for Peptidyl Disruptor Molecule against c-MYC-USP37 Complex. Molecules (Basel, Switzerland) 3 36985413
2025 USP37 prevents premature disassembly of stressed replisomes by TRAIP. Nature communications 2 40533495
2025 USP37 as a novel regulator of NRF2 protein stability and chemoresistance in HCC. Discover oncology 1 40080254
2025 USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance. Nucleic acids research 1 40548939
2024 Ubiquitin specific peptidase (USP37) mediated effects in microscaffold-encapsulated cells: a comprehensive study on growth, proliferation and EMT. RSC advances 1 38352690
2024 USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination. bioRxiv : the preprint server for biology 1 39282338
2026 The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. Cell systems 0 41633365
2026 CHK2-USP37 axis stabilizes FOXO4 to sustain senescence and evade apoptosis. Proceedings of the National Academy of Sciences of the United States of America 0 41980094
2025 The CENPN/STAT3/USP37 signaling axis promotes invasion, migration and metastasis in nasopharyngeal carcinoma. Frontiers in oncology 0 40458725
2025 An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer. Frontiers in cell and developmental biology 0 40926837
2025 Identification of Raptor and GLI1 as USP37 substrates highlight its context-specific function in medulloblastoma cells. Oncogene 0 41408466
2024 USP37 promotes diffuse large B-cell lymphoma progression by deubiquitinating and stabilizing c-myc. Journal of molecular histology 0 39722070