Affinage

SPOP

Speckle-type POZ protein · UniProt O43791

Length
374 aa
Mass
42.1 kDa
Annotated
2026-04-28
100 papers in source corpus 66 papers cited in narrative 65 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPOP is the substrate-recognition subunit of the CUL3-RING E3 ubiquitin ligase complex, serving as a central hub that targets a broad array of substrates for ubiquitination to regulate signaling in development, DNA repair, immune responses, and cancer. Its N-terminal MATH domain recognizes Ser/Thr-rich degron motifs (SBC motifs) in substrates—including AR, BRD2/3/4, ERG, PD-L1, NANOG, Gli3, MYD88, 53BP1, Geminin, and many others—often in a phosphorylation-dependent manner controlled by upstream kinases (CK1, GSK3β, ATM), while its BTB domain mediates CUL3 binding and dimerization and its BACK domain drives higher-order oligomerization into liquid-like nuclear speckles that enhance ubiquitination efficiency (PMID:19818708, PMID:27220849, PMID:36693379). SPOP catalyzes both K48-linked degradative and K27/K29-linked non-degradative polyubiquitination depending on substrate context: degradative ubiquitination controls turnover of AR, BRD4, PD-L1, GLP, and SETD2, while non-degradative ubiquitination regulates INF2 localization, Geminin licensing activity, p62 phase separation, and Myddosome assembly (PMID:24508459, PMID:28805820, PMID:29160310, PMID:34599168, PMID:31776466, PMID:34987184, PMID:28448495). Prostate cancer-associated SPOP mutations cluster in the MATH domain and impair substrate binding, whereas endometrial cancer mutations at oligomerization interfaces confer gain-of-function effects, and upstream kinases (AURKA, LIMK2, CDK4) and O-GlcNAcylation regulate SPOP stability and localization to modulate its activity in a context-dependent manner (PMID:28805821, PMID:57, PMID:33158056, PMID:36604567).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 Medium

    Establishing that SPOP is a nuclear speckle protein whose localization depends on both its POZ/BTB and MATH domains resolved the basic subcellular context of SPOP function.

    Evidence Deletion analysis and immunofluorescence in COS7 cells

    PMID:9414087

    Open questions at the time
    • No functional role identified
    • Nuclear speckle composition and dynamics not characterized
  2. 2009 High

    Structural determination of SPOP as a substrate adaptor for CUL3-RING E3 ligase defined its modular architecture—MATH domain for SBC degron recognition, BTB/3-box for CUL3 binding and dimerization—and explained how flexible MATH-BTB linkage enables engagement of multiple degrons within a single substrate.

    Evidence X-ray crystallography, SAXS, SEC-MALS, and biochemical reconstitution

    PMID:19818708

    Open questions at the time
    • Higher-order oligomerization beyond dimer not yet resolved
    • Full-length structure unavailable
  3. 2014 High

    Identification of androgen receptor (AR) as a direct SPOP substrate, with SBC degrons in the AR hinge domain, established the mechanistic link between SPOP loss-of-function mutations and AR-driven prostate cancer, and explained how AR splice variants escape SPOP-mediated degradation.

    Evidence Co-IP, ubiquitination assays, protein half-life analysis, xenograft models, and SPOP prostate-specific knockout mice

    PMID:24508459 PMID:25274033

    Open questions at the time
    • Mechanism of androgen-regulated SPOP-AR interaction not fully resolved
    • Contribution of individual AR degrons not dissected
  4. 2016 High

    Demonstrating that SPOP higher-order oligomerization through BTB (dimer) and BACK (linear oligomer) domains drives liquid nuclear speckle formation and enhances ubiquitination efficiency revealed a phase-separation-based mechanism for concentrating E3 ligase activity.

    Evidence Live-cell imaging, FRAP, analytical ultracentrifugation, SEC-MALS, and ubiquitination assays with oligomerization-deficient mutants

    PMID:27220849

    Open questions at the time
    • How substrates with few SBC motifs are processed outside speckles only partially addressed
    • Regulation of oligomerization dynamics unclear
  5. 2017 High

    Discovery that SPOP ubiquitinates BET proteins (BRD2/3/4) for degradation, and that prostate cancer versus endometrial cancer SPOP mutations have opposite effects—loss-of-function versus gain-of-function on the same substrates—established a paradigm of tissue-specific oncogenic consequences of SPOP mutations.

    Evidence Ubiquitin landscape proteomics, Co-IP, ubiquitination assays, organoid models, and patient specimens across three independent studies

    PMID:28805820 PMID:28805821 PMID:28805822

    Open questions at the time
    • Structural basis of gain-of-function endometrial mutations not yet defined at this point
    • How tissue context determines mutation outcome not mechanistically explained
  6. 2017 High

    Identification of PD-L1 as a direct SPOP substrate linked SPOP to immune checkpoint regulation: CDK4/6 phosphorylates SPOP to trigger its APC/C-mediated degradation, stabilizing PD-L1; SPOP loss-of-function mutations elevate PD-L1 and reduce tumor-infiltrating lymphocytes.

    Evidence Co-IP, ubiquitination assays, protein stability assays, mouse tumor models, CDK4/6 inhibitor treatment, patient specimens

    PMID:29160310

    Open questions at the time
    • Whether SPOP regulates PD-L1 transcriptionally (via IRF1) versus post-translationally in different tissues not yet integrated
  7. 2017 High

    Demonstration that SPOP catalyzes non-degradative polyubiquitination of INF2, reducing its ER localization and inhibiting mitochondrial fission, revealed that SPOP's output extends beyond substrate degradation to include spatial regulation of organelle dynamics.

    Evidence Co-IP, ubiquitination assay, fluorescence live-cell imaging of mitochondrial morphology

    PMID:28448495

    Open questions at the time
    • Ubiquitin chain linkage type for INF2 not fully characterized at this point
    • Physiological relevance of SPOP-INF2 axis outside cancer unclear
  8. 2019 High

    Multiple studies converged to establish MYD88 as a key SPOP substrate in innate immunity: SPOP ubiquitinates MYD88 to disrupt Myddosome assembly and NF-κB activation, and Spop-deficient mice develop lethal hyper-inflammation and susceptibility to infection.

    Evidence Proteomics-based substrate identification, Co-IP, ubiquitination assays, Spop KO mouse models with infection and inflammation phenotyping

    PMID:31406379 PMID:31776466 PMID:32365080

    Open questions at the time
    • Whether SPOP-MYD88 axis is degradative or non-degradative shows discrepancy between studies
    • Stimulus-dependent nuclear-cytoplasmic shuttling of SPOP for MYD88 targeting not fully resolved
  9. 2021 High

    ATM-dependent phosphorylation of SPOP was shown to trigger conformational changes that stabilize SPOP-53BP1 interaction, leading to 53BP1 polyubiquitination and p97-mediated extraction from chromatin to promote HR over NHEJ, placing SPOP as a regulated switch in DNA repair pathway choice.

    Evidence X-ray crystallography of phospho-SPOP, Co-IP, ubiquitination assays, HR/NHEJ reporter assays, cell cycle analysis

    PMID:34144977

    Open questions at the time
    • Whether other ATM-phosphorylated SPOP substrates (e.g., HIPK2) use the same conformational switch unknown
    • In vivo validation of DNA repair pathway choice limited
  10. 2021 High

    K27-linked non-degradative ubiquitination of Geminin by SPOP was shown to prevent Cdt1-MCM interaction and suppress replication origin over-firing, establishing SPOP as a guardian of replication licensing fidelity; cancer-associated SPOP mutations cause replication stress.

    Evidence Co-IP, K27-linkage-specific ubiquitination assays, replication assays in cancer cell models

    PMID:34599168

    Open questions at the time
    • How SPOP-Geminin axis is cell-cycle regulated not fully defined
    • Whether replication stress from SPOP mutation contributes to mutation signature unknown
  11. 2022 High

    SPOP was shown to non-degradatively ubiquitinate p62/SQSTM1 at K420, suppressing p62 phase condensation, dimerization, and autophagy flux, and relieving Keap1 sequestration to restrain Nrf2 antioxidant signaling, broadening SPOP's role to cytoplasmic quality control.

    Evidence Site-specific ubiquitination assays, autophagy flux assays, phase separation assays, Nrf2 reporter assays

    PMID:34987184

    Open questions at the time
    • Physiological triggers for cytoplasmic SPOP engagement with p62 unclear
    • Relationship to SPOP nuclear speckle dynamics not addressed
  12. 2023 High

    Crystal structure of oligomeric SPOP revealed new self-assembly interfaces beyond the known BTB dimer and BACK domain, and showed that many endometrial cancer mutations map to these interfaces, providing the first structural explanation for gain-of-function SPOP mutations acting through altered oligomerization rather than substrate binding.

    Evidence X-ray crystallography of oligomeric SPOP, biochemical characterization, cancer mutation mapping

    PMID:36693379

    Open questions at the time
    • Functional consequences of specific oligomerization mutants on substrate selectivity not fully tested
    • No cryo-EM or in-cell structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the full substrate repertoire and how substrate priority is determined in vivo; the structural basis of chain-type selectivity (K48 vs K27 vs K63); how nuclear–cytoplasmic shuttling is dynamically regulated; and whether SPOP mutations create therapeutic vulnerabilities beyond BET and CDK4/6 inhibitors.
  • No systematic quantitative comparison of substrate affinities in a single system
  • Structural basis for ubiquitin chain-type selectivity unknown
  • Full-length oligomeric SPOP-CUL3-RBX1 structure not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 21 GO:0060090 molecular adaptor activity 5
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 11 R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 1 R-HSA-9612973 Autophagy 1
Partners
53BP1ARBRD4CUL3G3BP1GLI3MYD88PD-L1
Complex memberships
CUL3-RBX1-SPOP E3 ligase

Evidence

Reading pass · 65 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SPOP is a nuclear speckle-type protein whose localization to nuclear speckles requires both the POZ domain and the evolutionarily conserved N-terminal region (MATH domain); it co-localizes with the splicing factor snRNP B'/B. Deletion analysis, immunofluorescence, transfection in COS7 cells FEBS letters Medium 9414087
2002 SPOP MATH domain directly binds the putative leucine zipper domain of macroH2A1.2, identifying macroH2A1.2 as a binding partner of SPOP. Yeast two-hybrid, GST pull-down Biochimica et biophysica acta Medium 12183056
2007 The BTB/POZ domain of SPOP is required for its pro-apoptotic function in HeLa cells; overexpression of the C-terminal BTB/POZ-containing fragment is sufficient to induce apoptosis. Overexpression of deletion mutants, apoptosis assays in HeLa cells BioFactors Low 18997279
2008 SPOP MATH domain interacts with the AF-2 domain of ERα and is required for CUL3-based E3 ubiquitin ligase-mediated ubiquitination and transcriptional repression of ERα. Co-immunoprecipitation, ubiquitination assay, transactivation reporter assay in HEK293 cells Molecules and cells Medium 18414007
2009 SPOP functions as a substrate adaptor in a CUL3-RING E3 ligase; its MATH domain binds a defined SPOP-binding consensus (SBC) motif in substrates (Puc phosphatase, Ci transcription factor, macroH2A); a conserved helical '3-box' C-terminal of the BTB domain mediates CUL3 binding; SPOP dimerizes through BTB and 3-box, and structural flexibility between MATH and BTB/3-box allows engagement of multiple SBCs within a single substrate. X-ray crystallography, SAXS, biochemical reconstitution, SEC-MALS Molecular cell High 19818708
2011 SPOP (in complex with CUL3/Rbx1) ubiquitinates SRC-3/AIB1 in a phosphorylation-dependent manner; Casein kinase Iε phosphorylates S102 within the SRC-3 degron to promote SPOP-dependent turnover. SPOP knockdown stabilizes SRC-3 and promotes oncogenic signaling. Co-immunoprecipitation, in vivo/in vitro ubiquitination assay, shRNA knockdown, overexpression, tumorigenesis assays Oncogene High 21577200
2014 SPOP recognizes a Ser/Thr-rich degron in the hinge domain of full-length androgen receptor (AR) and promotes AR ubiquitination and proteasomal degradation, thereby inhibiting AR-mediated transcription. AR splice variants lacking the hinge domain escape SPOP-mediated degradation. Prostate cancer-associated SPOP mutants cannot bind AR. Androgens antagonize and antiandrogens promote SPOP-mediated AR degradation. Co-immunoprecipitation, ubiquitination assay, protein half-life analysis, luciferase reporter, cell growth assays, xenograft models Cell reports High 24508459
2014 SPOP recognizes a Ser/Thr-rich degron in the transactivation domain of DDIT3/CHOP and promotes its ubiquitination and proteasomal degradation. Prostate cancer-associated SPOP mutants are defective in DDIT3 degradation. Co-immunoprecipitation, ubiquitination assay, Western blot, degron mutagenesis Human mutation Medium 24990631
2014 SPOP (via its MATH domain) directly binds the SPOP-binding motif in the hinge region of AR and promotes AR ubiquitination/degradation; loss of SPOP function via mutations constitutes an AR axis-centric mechanism of prostate cancer pathogenesis. Gene expression profiling, Co-immunoprecipitation, ubiquitination assay, xenograft models, mouse prostate SPOP knockout Cancer research High 25274033
2015 SPOP promotes ubiquitination and degradation of the ERG oncoprotein via CUL3-based E3 ligase; truncated ERG encoded by the TMPRSS2-ERG fusion escapes SPOP-mediated destruction. CKI-mediated phosphorylation modulates the SPOP/ERG interaction. Prostate cancer-associated SPOP mutants are deficient in promoting ERG ubiquitination. Co-immunoprecipitation, ubiquitination assay, protein stability analysis, kinase assay, prostate cancer models Molecular cell High 26344095
2015 SPOP-CUL3-RBX1 E3 ligase recognizes multiple Ser/Thr-rich degrons in the AF2 domain of ERα and triggers its ubiquitin-proteasomal degradation; endometrial cancer-associated SPOP mutants are defective in ERα degradation; SPOP participates in estrogen-induced ERα degradation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, degron mutagenesis, cell growth assays Cell death & disease Medium 25766326
2016 SPOP higher-order oligomerization is required for its localization to liquid nuclear speckles; SPOP oligomerizes through its BTB domain (dimer) and BACK domain (linear oligomers); self-association-deficient SPOP mutants show diffuse nuclear distribution; higher-order oligomerization stimulates CRL3-SPOP ubiquitination efficiency for Gli3. Live-cell imaging, FRAP, analytical ultracentrifugation, SEC-MALS, ubiquitination assays, mutational analysis The EMBO journal High 27220849
2016 SPOP is an important positive regulator of Indian Hedgehog (Ihh) signaling during skeletal development; Spop directly targets the Gli3 repressor (not Gli2) for ubiquitination and degradation; loss of Spop in mice increases Gli3 levels and suppresses Ihh target genes, causing chondrocyte and osteoblast differentiation defects that are rescued by reducing Gli3 dosage. Mouse genetic models (Spop-null and conditional KO), ubiquitination assay, in vivo epistasis (Gli3 dosage rescue) PNAS High 27930311
2016 SPOP promotes polyubiquitination and degradation of SETD2, thereby controlling H3K36me3 levels and H3K36me3-coupled alternative splicing genome-wide. Co-immunoprecipitation, in vivo and in vitro ubiquitination assays, ChIP-Seq, RNA-Seq Nucleic acids research High 27614073
2016 SPOP promotes polyubiquitination and proteasomal degradation of the Cdc20 oncoprotein in a degron-dependent manner; prostate cancer-derived SPOP mutants fail to interact with Cdc20, leading to its accumulation and resistance to pharmacological Cdc20 inhibition. Co-immunoprecipitation, ubiquitination assay, protein half-life assay, degron mutagenesis Cancer letters Medium 27780719
2016 In clear-cell renal cell carcinoma, cytoplasmic SPOP promotes β-catenin protein stabilization and nuclear translocation, elevating TCF4 and ZEB1 to drive EMT and invasion, representing an oncogenic (context-dependent) role of SPOP. Co-IP, Western blot, reporter assays, siRNA knockdown, invasion assays International journal of oncology Low 27572476
2016 Small molecules targeting the SPOP-substrate protein interaction surface inhibit oncogenic cytoplasmic SPOP signaling and selectively kill clear-cell renal cell carcinoma cells dependent on cytoplasmic SPOP. Structure-based drug design, in vitro binding assays, cell viability assays, SPOP-substrate interaction inhibition Cancer cell Medium 27622336
2017 CUL3-SPOP E3 ligase ubiquitinates PD-L1 to promote its proteasomal degradation; CDK4/6-mediated phosphorylation of SPOP promotes SPOP degradation by APC/C-FZR1, thereby stabilizing PD-L1; loss-of-function SPOP mutations impair PD-L1 ubiquitination, elevate PD-L1, and reduce tumor-infiltrating lymphocytes. Co-immunoprecipitation, ubiquitination assays, protein stability assays, mouse tumor models, patient specimens, CDK4/6 inhibitor treatment Nature High 29160310
2017 SPOP ubiquitinates BRD2, BRD3, and BRD4 for proteasomal degradation by recognizing a common degron motif; prostate cancer-associated SPOP mutants show impaired binding to BET proteins, causing their accumulation and resistance to BET inhibitors; BRD4 stabilization activates RAC1 and AKT-mTORC1 signaling. Co-immunoprecipitation, ubiquitination assay, protein half-life analysis, transcriptome/cistrome analysis, organoid models, patient specimens Nature medicine High 28805820 28805821 28805822
2017 Endometrial cancer-associated SPOP mutants preferentially degrade BET proteins (BRD2/3/4), whereas prostate cancer-specific SPOP mutants impair BET degradation, revealing opposing gain-of-function and loss-of-function effects of cancer-type-specific SPOP mutations on the same substrates. Ubiquitin landscape proteomics, Co-immunoprecipitation, ubiquitination assay, cell line and organoid models Nature medicine High 28805821
2017 SPOP ubiquitinates and degrades EglN2 prolyl hydroxylase; AR transcriptionally upregulates EglN2, and SPOP loss-of-function mutations or AR amplification accumulate EglN2 to drive prostate cancer growth. Co-immunoprecipitation, ubiquitination assay, protein half-life analysis, chromatin immunoprecipitation, xenograft models Cancer letters Medium 28089830
2017 SPOP recognizes a Ser/Thr-rich motif in the C-terminal region of INF2 and triggers atypical (non-degradative) polyubiquitination of INF2, reducing INF2 localization at the ER and mitochondrially associated DRP1 puncta, thereby inhibiting mitochondrial fission; prostate cancer-associated SPOP mutants have dominant-negative effects that increase INF2 ER localization and promote mitochondrial fission. Co-immunoprecipitation, ubiquitination assay, fluorescence live-cell imaging, mitochondrial morphology analysis, prostate cancer cell models PLoS genetics High 28448495
2017 SPOP mutation drives prostate tumorigenesis in vivo by activating both PI3K/mTOR and AR signaling pathways, effectively uncoupling the normal negative feedback between these two pathways in the setting of Pten loss. Conditional mouse model, prostate organoids, gene expression analysis, patient samples Cancer cell High 28292441
2017 The CUL3-SPOP-DAXX axis regulates VEGFR2 mRNA expression in vascular endothelial cells; SPOP targets DAXX for ubiquitination and degradation, and loss of SPOP/CUL3 increases DAXX and decreases VEGFR2, NOTCH1, DLL4, and NRP1 levels. siRNA knockdown, Co-immunoprecipitation, Western blot, VEGFR2 expression analysis Scientific reports Medium 28216678
2014 SPOP is recruited to DNA double-strand break (DSB) sites, forms nuclear foci that co-localize with γ-H2AX, interacts with ATM in response to DNA damage in an ATM kinase activity-dependent manner, and SPOP knockdown impairs the DNA damage response and causes hypersensitivity to ionizing radiation. Immunofluorescence (foci formation), Co-immunoprecipitation, ATM inhibitor, siRNA knockdown, clonogenic survival assay Carcinogenesis Medium 24451148
2018 SPOP recognizes multiple Ser/Thr-rich degrons in ATF2 and promotes its ubiquitination and proteasomal degradation; prostate cancer-associated SPOP mutants are defective in ATF2 degradation, resulting in increased cell proliferation, migration, and invasion. Yeast two-hybrid, Co-immunoprecipitation, ubiquitination assay, degron mutagenesis, Transwell assay Journal of experimental & clinical cancer research Medium 29996942
2018 TRIM28 interacts with TRIM24 to prevent SPOP-mediated ubiquitination and degradation of TRIM24, thereby stabilizing TRIM24 and augmenting AR signaling in prostate cancer. Co-immunoprecipitation, ubiquitination assay, ChIP, protein half-life analysis, xenograft models Nature communications High 30479348
2018 AMPK-BRAF signal axis controls SPOP-mediated NANOG degradation through phosphorylation of NANOG at Ser68, which blocks the SPOP-NANOG interaction; SPOP promotes NANOG polyubiquitination and degradation; cancer-associated SPOP mutations or S68Y NANOG mutation abrogate this process, elevating prostate cancer stemness. Co-immunoprecipitation, ubiquitination assay, kinase assay, stem cell assays, in vivo tumor models Developmental cell High 30595535 30595538
2018 SPOP promotes Nanog polyubiquitination and degradation; the Pin1 oncoprotein acts as an upstream regulator that impairs Nanog recognition by SPOP, thereby stabilizing Nanog; Pin1 inhibitors promote SPOP-mediated Nanog destruction. Co-immunoprecipitation, ubiquitination assay, degron mutagenesis (S68Y), protein half-life, stem cell phenotype assays, patient samples Developmental cell High 30595538
2018 Crystal structure of the SPOP MATH domain bound to the Pdx1 degron peptide reveals an extended binding interface; phosphorylation of Pdx1 within this interface reduces its affinity for SPOP, providing a mechanism for phosphorylation-dependent regulation of Pdx1 ubiquitination. X-ray crystallography, ITC, NMR Structure High 30449689
2019 Wild-type SPOP ubiquitinates and promotes proteasomal degradation of Caprin1 (a stress granule nucleating protein); prostate cancer-associated SPOP mutants fail to degrade Caprin1, leading to elevated stress granule assembly, enhanced cell survival under stress, and resistance to docetaxel. Yeast two-hybrid, Co-immunoprecipitation, ubiquitination assay, stress granule imaging, xenograft models, patient specimens Molecular cancer High 31771591
2019 EGF-MEK-ERK-mediated phosphorylation of ILF3 prevents SPOP-mediated polyubiquitination and degradation of ILF3 in colorectal cancer, allowing ILF3 to stabilize SGOC pathway gene mRNAs and promote tumor growth. Co-immunoprecipitation, ubiquitination assay, kinase pathway inhibitor experiments, patient specimens Cell research Medium 31772275
2019 SPOP ubiquitinates MYD88 in a non-degradative manner to disrupt Myddosome assembly and downstream NF-κB activation; lymphoid malignancy-associated SPOP mutants show impaired binding to MyD88; SPOP suppresses DLBCL cell growth in vitro and in vivo through inhibition of MyD88/NF-κB signaling. Co-immunoprecipitation, ubiquitination assay, NF-κB reporter assay, xenograft model Leukemia High 31776466
2019 SPOP ubiquitinates MYD88 and promotes its degradation via the proteasome to suppress innate immune inflammatory responses; Spop-deficient mice are more susceptible to Salmonella infection. Co-immunoprecipitation, ubiquitination assay, Spop KO mouse model, infection model PLoS pathogens High 32365080
2019 SPOP ubiquitinates MYD88 to restrain inflammatory activation of hematopoietic stem cells; SPOP-deficient mice exhibit unresolved systemic inflammation and a lethal hyper-inflammatory phenotype. Proteomics identified MYD88 as a direct SPOP substrate. Mass spectrometry proteomics, Co-immunoprecipitation, ubiquitination assay, Spop KO mouse model, inflammation phenotyping Nature immunology High 31406379
2019 SPOP depletion in human erythroid cells reactivates fetal hemoglobin (HbF) expression independently of BCL11A and LRF, identifying SPOP/CUL3 as a novel HbF repressor pathway. SPOP dominant-negative overexpression also raises fetal globin levels. CRISPR-Cas9 domain-focused screen, shRNA knockdown, transcriptome and proteome analysis Blood advances Medium 31126914
2020 TLR4 activation triggers translocation of SPOP from nucleus to cytoplasm; SPOP binds MyD88 and disrupts MyD88 self-association (Myddosome assembly), thereby suppressing downstream IRAK4/IRAK1/IRAK2 recruitment and NF-κB activation and reducing inflammatory cytokine production. Co-immunoprecipitation, overexpression/knockdown, NF-κB reporter assay, cytokine ELISA, immunofluorescence Cellular & molecular immunology Medium 32235916
2020 SPOP promotes ubiquitination and proteasomal degradation of LATS1 (Hippo pathway component) in kidney cancer; this is CUL3-dependent and degron-mediated, and promotes kidney cancer cell proliferation and invasion. Co-immunoprecipitation, ubiquitination assay, protein half-life analysis, cell proliferation assays EBioMedicine Medium 32460168
2021 ATM kinase phosphorylates SPOP in response to DNA damage, causing a conformational change (revealed by X-ray crystallography) that stabilizes SPOP-53BP1 interaction; SPOP then induces polyubiquitination of 53BP1, triggering p97/VCP-mediated extraction of 53BP1 from chromatin, thereby promoting homologous recombination over NHEJ during S phase. Cancer-derived SPOP mutations block interaction with 53BP1 and cause HR defects. X-ray crystallography, Co-immunoprecipitation, ubiquitination assay, SPOP phospho-mutants, HR/NHEJ reporter assays, cell cycle analysis Science advances High 34144977
2021 SPOP binds Geminin and promotes K27-linked non-degradative polyubiquitination of Geminin at K100 and K127, preventing Cdt1-MCM interaction and thereby suppressing DNA replication origin over-firing; cancer-associated SPOP mutations impair Geminin ubiquitination and induce replication stress and re-replication. Co-immunoprecipitation, ubiquitination assay with K27-linkage specificity, replication assays, cryo-EM/structural analysis cited, cancer cell models Nature communications High 34599168
2021 SPOP binds a functional SBC motif (315RATST319) in 17βHSD4 and promotes non-degradative K27- and K29-linked polyubiquitination, stabilizing 17βHSD4; this opposes SKP2-mediated K48-linked polyubiquitination and degradation. SGK3-mediated phosphorylation of S318 in the SBC blocks SPOP binding. Prostate cancer-associated SPOP mutations impair this interaction, causing 17βHSD4 degradation and increased intratumoral androgen synthesis. Co-immunoprecipitation, in vitro ubiquitination assay with linkage-specific analysis, kinase assay, prostate cancer cell and mouse models Cancer research High 33762355
2021 SPOP ubiquitinates PDK1 for proteasomal degradation in a CK1/GSK3β-mediated phosphorylation-dependent manner via a consensus degron; prostate cancer-associated SPOP mutations impair PDK1 degradation, activating AKT kinase. CRISPR-based E3 ligase screen, Co-immunoprecipitation, ubiquitination assay, in vitro kinase assay, mass spectrometry, xenograft models Molecular cancer High 34353330
2021 ATM phosphorylates SPOP at Ser119, which potentiates SPOP binding to HIPK2 and triggers non-degradative ubiquitination of HIPK2; this increases HIPK2 phosphorylation of HP1γ, promoting HP1γ dissociation from H3K9me3 to initiate DNA damage repair; prostate cancer-associated SPOP mutations abrogate this axis, causing genomic instability. Co-immunoprecipitation, ubiquitination assay, phosphorylation assays, ChIP, DNA repair assays, patient samples Nucleic acids research High 34133717
2021 SPOP promotes ubiquitination and degradation of EWS-FLI1 (Ewing sarcoma oncofusion) in a CK1-mediated phosphorylation-dependent (VTSSS degron) manner; OTUD7A is the opposing deubiquitinase that stabilizes EWS-FLI1; OTUD7A depletion reduces EWS-FLI1 and impedes Ewing sarcoma growth in vitro and in vivo. Co-immunoprecipitation, ubiquitination/deubiquitination assays, kinase assay, xenograft models, AI-based drug screen Advanced science High 34060252
2021 ERG transcription factor upregulates wild-type SPOP to dampen AR signaling and sustain ERG activity through ZMYND11 degradation; SPOP-mutant tumors stabilize ZMYND11 to repress ERG function and enable oncogenic AR signaling, explaining the synthetic sickness of ERG and SPOP alterations. Co-immunoprecipitation, ubiquitination assay, transcriptomics, ChIP, genetic models, patient cohorts Nature communications High 33531470
2021 G3BP1 acts as a competitive inhibitor of CUL3-SPOP by directly interacting with SPOP, blocking substrate access and promoting prostate cancer progression via AR signaling; AR directly transcriptionally upregulates G3BP1 in a feed-forward loop. Co-immunoprecipitation, ubiquitination assay, transcriptomics, ChIP, xenograft models, patient samples Nature communications High 34795264
2021 Intrinsically disordered Pdx1 with only two SPOP-binding motifs (insufficient for phase separation with SPOP) redirects SPOP from nuclear speckles to the diffuse nucleoplasm; SPOP-mediated ubiquitination of Pdx1 occurs in the nucleoplasm and requires both SB motifs for efficient turnover. Substrate properties thus dictate subnuclear location of SPOP ubiquitination activity. Live-cell fluorescence imaging, FRAP, mutagenesis, ubiquitination assay, NMR Journal of Biological Chemistry High 33894201
2021 AURKA directly phosphorylates SPOP at three sites, causing SPOP ubiquitylation and degradation, thereby stabilizing AR, ARv7, and c-Myc and promoting castration-resistant prostate cancer; SPOP reciprocally degrades AURKA in a feedback loop; phospho-resistant SPOP abrogates tumorigenesis in vivo. Direct substrate identification technique, in vitro kinase assay, Co-immunoprecipitation, ubiquitination assay, xenograft models Cancers Medium 33158056
2020 LIMK2 directly phosphorylates SPOP at three sites, promoting SPOP ubiquitylation and degradation, which stabilizes AR, ARv7, and c-Myc; SPOP promotes LIMK2 ubiquitylation in a feedback loop; phospho-resistant SPOP completely suppresses tumorigenesis in vivo. Direct substrate identification, in vitro kinase assay, Co-immunoprecipitation, ubiquitination assay, xenograft models British journal of cancer Medium 33311589
2021 SPOP promotes CK1/GSK3β-phosphorylation-dependent ubiquitination and proteasomal degradation of CDCA5 in prostate cancer; prostate cancer-associated SPOP mutations impair CDCA5 degradation, causing G2/M arrest evasion and AKT pathway activation. Co-immunoprecipitation, ubiquitination assay, protein half-life analysis, cell cycle analysis, AKT pathway assays Neoplasia Medium 34509929
2021 SPOP binds to and promotes proteasomal degradation of STING1; prostate cancer-associated SPOP mutations result in STING1 upregulation and non-canonical NF-κB signaling; PARP inhibitor shifts this to canonical cGAS-STING-IFNβ signaling in SPOP-mutant CRPC. Co-immunoprecipitation, proteomics analysis, cell line models, in vivo xenograft models, transcriptomics Clinical cancer research Medium 37581614
2021 SPOP mutation induces stabilization of histone methyltransferase GLP (and its partner G9a), leading to aberrant genome-wide DNA hypermethylation; SPOP binds and promotes polyubiquitination and degradation of GLP; hypermethylation of tumor suppressor gene promoters (FOXO3, GATA5, NDRG1) is a consequence. Co-immunoprecipitation, ubiquitination assay, DNA methylome sequencing (RRBS/WGBS), 5-azacytidine rescue, patient specimens Nature communications High 34588438
2022 Cytoplasmic SPOP binds p62/SQSTM1 and promotes non-degradative K420 polyubiquitination, which decreases p62 puncta formation, liquid-liquid phase condensation, dimerization, and ubiquitin-binding capacity, thereby suppressing p62-dependent autophagy; SPOP also relieves p62-mediated Keap1 sequestration to reduce Nrf2 activation. PCa-associated SPOP mutants cannot ubiquitinate p62. Co-immunoprecipitation, ubiquitination assay with site-specific mutagenesis, autophagy flux assays, phase separation assays, Nrf2/antioxidant reporter assays Cell death and differentiation High 34987184
2022 MLN4924 (neddylation inhibitor) inactivates CRL3-SPOP, causing accumulation of glutamine transporter ASCT2/SLC1A5; SPOP directly promotes ASCT2 ubiquitylation and its own auto-ubiquitylation upon glutamine deprivation, inversely regulating glutamine uptake and metabolism in breast cancer. Co-immunoprecipitation, in vitro ubiquitination assay, MLN4924 treatment, ASCT2 knockdown rescue, tumor growth assays Nature communications High 35641493
2022 SPOP negatively regulates PD-L1 expression at the transcriptional level in endometrial cancer by binding IRF1 and triggering its ubiquitin-proteasomal degradation, thereby suppressing IRF1-mediated PD-L1 transcription; EC-associated SPOP mutants lose this capacity. Co-immunoprecipitation, ubiquitination assay, luciferase reporter, qRT-PCR, xenograft models, patient specimens Cell death and differentiation High 36481790
2022 SPOP promotes K63- and K48-linked ubiquitination of TWIST1 predominantly at K73, destabilizing TWIST1 and suppressing EMT-driven breast cancer cell migration, invasion, and lung metastasis. Co-immunoprecipitation, ubiquitination assay with linkage analysis, mutagenesis, migration/invasion assays, in vivo metastasis model Cell death discovery Medium 36115849
2022 ATR inhibition activates the CDK1-SPOP axis, leading to destabilization of PD-L1 protein and triggering cGAS-STING-IFNβ-mediated apoptosis in prostate cancer; this is distinct from PARP inhibitor effects. Cell line treatment with ATR inhibitor, Western blotting for PD-L1, cGAS-STING pathway analysis, syngeneic mouse model with single-cell RNA-seq Clinical cancer research Medium 34168048
2023 Crystal structure of oligomeric SPOP reveals new self-assembly interfaces (beyond BTB dimer and BACK domain); many endometrial cancer mutations localize to these new interfaces, promoting enhanced self-association or altered stability and activity — providing molecular mechanism for gain-of-function cancer mutations not in the substrate-binding MATH domain. X-ray crystallography of oligomeric SPOP, biochemical characterization, cancer mutation mapping Molecular cell High 36693379
2023 O-GlcNAcylation of SPOP at Ser96 by OGT increases nuclear positioning of SPOP in hepatoma cells, reducing cytoplasmic SPOP-mediated ubiquitination of Nogo-B and promoting HCC progression; S96A mutation increases cytoplasmic SPOP and restores Nogo-B ubiquitination. O-GlcNAcylation assay, Co-immunoprecipitation, ubiquitination assay, mutagenesis, subcellular fractionation, in vivo tumor models Oncogene Medium 36604567
2024 SPOP ubiquitinates IRF2BP2 for degradation; a HCC-derived SPOP M35L mutation shows increased affinity to IRF2BP2 compared to wild-type SPOP, converting SPOP from tumor suppressor to oncoprotein in HCC, demonstrating that MATH domain point mutations can reprogram substrate preference rather than simply disrupting interactions. Co-immunoprecipitation, ubiquitination assay, affinity measurements, cell proliferation and metastasis assays Cell death & disease Medium 38409107
2024 BCLAF1 interacts with SPOP via an SBC motif and competitively inhibits SPOP-PD-L1 interaction and subsequent PD-L1 ubiquitination and degradation in hepatocellular carcinoma, thereby stabilizing PD-L1 and enabling immune escape. Co-immunoprecipitation, ubiquitination assay, SBC motif mutagenesis, T cell co-culture cytotoxicity assay, tumor models Cellular and molecular life sciences Medium 38340178
2024 CSN6 antagonizes SPOP ubiquitin ligase to stabilize HMGCS1 in hepatocellular carcinoma; SPOP promotes HMGCS1 degradation, and CSN6 elevation prevents this, activating YAP1 to promote tumor growth. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, orthotopic liver cancer models, patient-derived xenografts Advanced science Medium 38308184
2021 SPOP promotes GLI3 ubiquitination and proteasomal degradation in prostate cancer; SPOP driver mutations abrogate GLI3 degradation, leading to GLI3 stabilization; GLI3 physically interacts with AR and activates AR-dependent gene expression to promote castration-resistant prostate cancer growth. Co-immunoprecipitation, ubiquitination assay, xenograft models, transcriptomics Molecular cancer research Medium 34610962
2019 SPOP in pancreatic mesenchyme, together with Sufu, controls Hedgehog signaling by targeting Gli2-mediated activation; loss of Spop and Sufu in pancreatic stromal cells impairs pancreatic growth and beta cell genesis through Gli2-mediated upregulation of Wnt ligands. Mouse genetic models (stroma-specific Spop and Sufu KO), transcriptome analysis, organoid inhibitor experiments Nature communications Medium 31604927
2017 Spop negatively regulates Gli3 activator activity and Shh signaling in mouse spinal cord dorsoventral patterning; loss of Spop suppresses the Gli2 mutant floor plate phenotype by restoring Gli3 activator activity, demonstrating epistasis between Spop, Gli2, and Gli3 in ventral spinal cord specification. Mouse genetic models, in vivo epistasis (Spop;Gli2 and Spop;Gli1;Sufu double mutants), protein level analysis Developmental biology Medium 28412462

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 843 29160310
2009 Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Molecular cell 410 19818708
2017 Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Nature medicine 279 28805820
2017 Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nature medicine 250 28805822
2014 Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell reports 230 24508459
2015 SPOP Promotes Ubiquitination and Degradation of the ERG Oncoprotein to Suppress Prostate Cancer Progression. Molecular cell 178 26344095
2016 Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles. The EMBO journal 174 27220849
2017 SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer cell 163 28292441
2017 Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors. Nature medicine 156 28805821
2014 Androgen receptor is the key transcriptional mediator of the tumor suppressor SPOP in prostate cancer. Cancer research 155 25274033
2011 Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis of the oncogenic co-activator SRC-3/AIB1. Oncogene 148 21577200
2018 SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity. Clinical cancer research : an official journal of the American Association for Cancer Research 120 30068710
2021 ATR Inhibition Induces CDK1-SPOP Signaling and Enhances Anti-PD-L1 Cytotoxicity in Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 114 34168048
1997 Identification of a novel nuclear speckle-type protein, SPOP. FEBS letters 109 9414087
2019 Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly. Molecular cancer 106 31771591
2018 TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression. Nature communications 99 30479348
2020 The emerging role of SPOP protein in tumorigenesis and cancer therapy. Molecular cancer 91 31901237
2019 ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer. Cell research 90 31772275
2020 The diverse roles of SPOP in prostate cancer and kidney cancer. Nature reviews. Urology 85 32355326
2022 SPOP mutations promote p62/SQSTM1-dependent autophagy and Nrf2 activation in prostate cancer. Cell death and differentiation 79 34987184
2020 SPOP and cancer: a systematic review. American journal of cancer research 75 32266086
2018 AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness. Developmental cell 75 30595535
2016 Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer. Cancer cell 75 27622336
2014 The emerging role of speckle-type POZ protein (SPOP) in cancer development. Drug discovery today 74 25058385
2019 The novel BET-CBP/p300 dual inhibitor NEO2734 is active in SPOP mutant and wild-type prostate cancer. EMBO molecular medicine 73 31559706
2021 SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions. Molecular cancer 70 34353330
2022 Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer cells. Nature communications 65 35641493
2016 SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. Nucleic acids research 65 27614073
2020 Association of SPOP Mutations with Outcomes in Men with De Novo Metastatic Castration-sensitive Prostate Cancer. European urology 64 32624276
2017 Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer. PLoS genetics 64 28448495
2018 SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression. Developmental cell 63 30595538
2014 SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer. Journal of experimental & clinical cancer research : CR 63 25204354
2022 SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis-Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 61 36088616
2019 The ubiquitin ligase adaptor SPOP in cancer. The FEBS journal 60 31495053
2015 Endometrial cancer-associated mutants of SPOP are defective in regulating estrogen receptor-α protein turnover. Cell death & disease 60 25766326
2021 SPOP and OTUD7A Control EWS-FLI1 Protein Stability to Govern Ewing Sarcoma Growth. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 59 34060252
2016 Spop promotes skeletal development and homeostasis by positively regulating Ihh signaling. Proceedings of the National Academy of Sciences of the United States of America 59 27930311
2023 Deregulation of SPOP in Cancer. Cancer research 55 36512624
2019 The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation. Nature immunology 53 31406379
2019 CRL3-SPOP ubiquitin ligase complex suppresses the growth of diffuse large B-cell lymphoma by negatively regulating the MyD88/NF-κB signaling. Leukemia 50 31776466
2018 SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression. Journal of experimental & clinical cancer research : CR 50 29996942
2022 SPOP mutations promote tumor immune escape in endometrial cancer via the IRF1-PD-L1 axis. Cell death and differentiation 49 36481790
2019 BET Inhibitors Potentiate Chemotherapy and Killing of SPOP-Mutant Colon Cancer Cells via Induction of DR5. Cancer research 48 30674532
2021 ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication. Science advances 47 34144977
2018 Dual inhibition of AKT-mTOR and AR signaling by targeting HDAC3 in PTEN- or SPOP-mutated prostate cancer. EMBO molecular medicine 47 29523594
2016 Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation. Cancer letters 46 27780719
2021 Clinical and genomic features of SPOP-mutant prostate cancer. The Prostate 44 34783071
2020 SPOP negatively regulates Toll-like receptor-induced inflammation by disrupting MyD88 self-association. Cellular & molecular immunology 42 32235916
2016 SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma. International journal of oncology 42 27572476
2014 Speckle-type POZ protein, SPOP, is involved in the DNA damage response. Carcinogenesis 42 24451148
2021 Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer. Nature communications 41 33531470
2020 SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression. EBioMedicine 41 32460168
2017 Tumor suppressor SPOP ubiquitinates and degrades EglN2 to compromise growth of prostate cancer cells. Cancer letters 41 28089830
2021 SPOP mutation induces DNA methylation via stabilizing GLP/G9a. Nature communications 40 34588438
2018 Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer. JCO precision oncology 40 30761387
2014 Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer. European journal of cancer (Oxford, England : 1990) 39 25204806
2018 miRNA-543 promotes cell migration and invasion by targeting SPOP in gastric cancer. OncoTargets and therapy 38 30174445
2020 SPOP promotes ubiquitination and degradation of MyD88 to suppress the innate immune response. PLoS pathogens 35 32365080
2018 The E2F1-miR-520/372/373-SPOP Axis Modulates Progression of Renal Carcinoma. Cancer research 34 30348808
2019 Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals. Nature communications 33 31604927
2024 CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 32 38308184
2021 Mutated SPOP E3 Ligase Promotes 17βHSD4 Protein Degradation to Drive Androgenesis and Prostate Cancer Progression. Cancer research 31 33762355
2021 G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer. Nature communications 31 34795264
2014 Destruction of DDIT3/CHOP protein by wild-type SPOP but not prostate cancer-associated mutants. Human mutation 31 24990631
2021 Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis. Nucleic acids research 30 34133717
2023 Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation. Molecular cell 29 36693379
2022 Tumor stem cell-derived exosomal microRNA-17-5p inhibits anti-tumor immunity in colorectal cancer via targeting SPOP and overexpressing PD-L1. Cell death discovery 29 35461336
2021 SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition. Nature communications 29 34599168
2024 BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma. Cellular and molecular life sciences : CMLS 28 38340178
2018 Functional roles of Speckle-Type Poz (SPOP) Protein in Genomic stability. Journal of Cancer 28 30271484
2017 Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the mouse spinal cord. Developmental biology 28 28412462
2002 MacroH2A1.2 binds the nuclear protein Spop. Biochimica et biophysica acta 28 12183056
2022 Novel insights into the SPOP E3 ubiquitin ligase: From the regulation of molecular mechanisms to tumorigenesis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 35364375
2022 CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein. Journal for immunotherapy of cancer 26 36198437
2017 The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells. Scientific reports 26 28216678
2020 LncRNA ADAMTS9-AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP. Journal of cellular and molecular medicine 25 32160650
2021 GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer. Molecular cancer research : MCR 24 34610962
2018 The Structure of the SPOP-Pdx1 Interface Reveals Insights into the Phosphorylation-Dependent Binding Regulation. Structure (London, England : 1993) 24 30449689
2023 O-GlcNAcylation of SPOP promotes carcinogenesis in hepatocellular carcinoma. Oncogene 23 36604567
2021 c-Myb facilitates immune escape of esophageal adenocarcinoma cells through the miR-145-5p/SPOP/PD-L1 axis. Clinical and translational medicine 23 34586738
2019 The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells. Blood advances 23 31126914
2023 SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor-Induced Growth Suppression. Clinical cancer research : an official journal of the American Association for Cancer Research 22 37581614
2022 Enhanced autophagy and NFE2L2/NRF2 pathway activation in SPOP mutation-driven prostate cancer. Autophagy 22 35438056
2024 SPOP downregulation promotes bladder cancer progression based on cancer cell-macrophage crosstalk via STAT3/CCL2/IL-6 axis and is regulated by VEZF1. Theranostics 21 39479456
2020 Structure-Activity Relationship of SPOP Inhibitors against Kidney Cancer. Journal of medicinal chemistry 21 32297747
2021 SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway. Neoplasia (New York, N.Y.) 20 34509929
2020 Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer. British journal of cancer 20 33311589
2021 Intrinsically disordered substrates dictate SPOP subnuclear localization and ubiquitination activity. The Journal of biological chemistry 19 33894201
2020 Molecular Interplay between AURKA and SPOP Dictates CRPC Pathogenesis via Androgen Receptor. Cancers 19 33158056
2019 MiR-373 promotes proliferation and metastasis of oral squamous cell carcinoma by targeting SPOP. European review for medical and pharmacological sciences 19 31298378
2022 ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression. Cell death and differentiation 18 35194188
2022 The speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing TWIST1. Cell death discovery 17 36115849
2020 S119N Mutation of the E3 Ubiquitin Ligase SPOP Suppresses SLC7A1 Degradation to Regulate Hepatoblastoma Progression. Molecular therapy oncolytics 17 33209975
2019 SPOP targets oncogenic protein ZBTB3 for destruction to suppress endometrial cancer. American journal of cancer research 17 31911863
2018 SPOP suppresses osteosarcoma invasion via PI3K/AKT/NF-κB signaling pathway. European review for medical and pharmacological sciences 17 29461588
2017 SPOP-mediated degradation of BRD4 dictates cellular sensitivity to BET inhibitors. Cell cycle (Georgetown, Tex.) 17 29108467
2008 Repression of transcriptional activity of estrogen receptor alpha by a Cullin3/SPOP ubiquitin E3 ligase complex. Molecules and cells 17 18414007
2020 The GPER1/SPOP axis mediates ubiquitination-dependent degradation of ERα to inhibit the growth of breast cancer induced by oestrogen. Cancer letters 16 33069770
2024 SPOP point mutations regulate substrate preference and affect its function. Cell death & disease 15 38409107
2007 BTB/POZ domain of speckle-type POZ protein (SPOP) confers proapoptotic function in HeLa cells. BioFactors (Oxford, England) 15 18997279