Affinage

SPOP

Speckle-type POZ protein · UniProt O43791

Length
374 aa
Mass
42.1 kDa
Annotated
2026-06-10
100 papers in source corpus 55 papers cited in narrative 55 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPOP is the substrate-recognition adaptor of a CUL3-RBX1 RING E3 ubiquitin ligase that selects substrates bearing Ser/Thr-rich degron motifs through its MATH domain, thereby controlling the abundance and activity of a broad array of nuclear regulators (PMID:24508459, PMID:23559371, PMID:25766326). Through its BTB and BACK domains SPOP self-assembles into higher-order oligomers that concentrate the ligase in liquid nuclear speckles, where ubiquitination of substrates such as Gli3 is most efficient; substrate valency itself can redistribute SPOP between speckles and the diffuse nucleoplasm (PMID:27220849, PMID:33894201), and crystallographic analysis of the oligomeric form maps cancer mutations to self-assembly interfaces (PMID:36693379). A dominant theme is the proteasomal destruction of transcriptional and signaling regulators—androgen receptor and its coactivator SRC-3, the ETS factor ERG, BET bromodomain proteins BRD2/3/4, c-MYC, ERα, the pluripotency factor Nanog, and the histone methyltransferases SETD2 and GLP—linking SPOP to nuclear receptor signaling, chromatin state, and proliferative control (PMID:28805820, PMID:28805822, PMID:24508459, PMID:23559371, PMID:26344095, PMID:27614073, PMID:30595538, PMID:30595535, PMID:28414305, PMID:34588438). Beyond canonical K48-linked degradation, SPOP also deposits non-degradative K27/K29-linked chains: it ubiquitinates Geminin to restrain replication origin re-firing, modifies INF2 to suppress mitochondrial fission, marks p62/SQSTM1 to inhibit autophagy and Nrf2 signaling, and stabilizes 17βHSD4 to limit androgen synthesis (PMID:34599168, PMID:28448495, PMID:34987184, PMID:33762355). In the DNA damage response, ATM-mediated phosphorylation of SPOP triggers a conformational switch that drives 53BP1 ubiquitination and chromatin extraction to favor homologous recombination, and SPOP loss produces a BRCA-like repair defect that sensitizes cells to PARP inhibition (PMID:34144977, PMID:26374986, PMID:34133717). SPOP activity is itself governed by upstream kinases and modifications—CDK4, AURKA, and LIMK2 phosphorylation drive SPOP turnover, while O-GlcNAcylation tunes its nuclear/cytoplasmic distribution—and cancer-associated MATH-domain mutations recurrent in prostate and endometrial tumors abolish substrate binding, broadly dysregulating these proteostatic programs (PMID:29160310, PMID:33158056, PMID:33311589, PMID:36604567).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 Low

    Before its E3 role was known, the question was what SPOP binds; the MATH domain was shown to engage a histone variant, hinting at a nuclear/chromatin-associated function.

    Evidence Yeast two-hybrid and GST pull-down mapping MATH-domain binding to macroH2A1.2

    PMID:12183056

    Open questions at the time
    • Interaction not confirmed in cells and no functional consequence established
    • No link to ubiquitination demonstrated
  2. 2013 High

    Establishing SPOP as a CUL3 substrate adaptor in cancer, SRC-3 was identified as a degradation target whose loss explains SPOP's suppression of androgen receptor activity.

    Evidence Co-IP and CUL3-dependent ubiquitination assays with prostate cancer mutant characterization

    PMID:23559371

    Open questions at the time
    • Degron not precisely mapped here
    • Did not address direct AR turnover
  3. 2014 High

    The defining recognition principle—a Ser/Thr-rich degron read by SPOP—was demonstrated by direct degradation of full-length AR and DDIT3/CHOP, with splice variants and cancer mutants escaping turnover.

    Evidence Degron mapping, Co-IP, ubiquitination assays, and growth assays in prostate cancer cells

    PMID:24508459 PMID:24990631

    Open questions at the time
    • Did not resolve which ubiquitin linkage types are used
    • In vivo physiological relevance not yet tested
  4. 2015 Medium

    SPOP was tied to genome integrity and to phospho-regulated substrate selection, showing ERG recognition is gated by CKI phosphorylation and that SPOP mutation produces a BRCA1-like HDR defect.

    Evidence Phosphorylation mapping and ubiquitination assays (ERG); transcriptional profiling, DNA repair assays, and PARP inhibitor sensitivity in mouse models

    PMID:26344095 PMID:26374986

    Open questions at the time
    • The direct repair substrate underlying the HDR defect was not defined in 2015
    • Mechanism connecting adaptor loss to repair gene expression unclear
  5. 2016 High

    The biophysical basis of SPOP function was established: BTB/BACK-driven higher-order oligomerization localizes the ligase to nuclear speckles and boosts ubiquitination efficiency, reframing speckles as ubiquitination hotspots.

    Evidence Analytical ultracentrifugation, live-cell imaging, in vitro ubiquitination of Gli3, and domain-mapping mutants

    PMID:27220849

    Open questions at the time
    • Did not address how individual substrates partition relative to speckles
    • Quantitative contribution of oligomerization to specific substrate turnover not measured
  6. 2016 High

    In vivo developmental and oncogenic roles were anchored by knockout genetics: Spop regulates Gli3 and Hedgehog-dependent skeletal development, and SETD2 turnover links SPOP to chromatin methylation and splicing.

    Evidence Spop-null/conditional mice with Gli3 dosage rescue; ChIP-Seq and splicing analysis for SETD2

    PMID:27614073 PMID:27930311

    Open questions at the time
    • Tissue-specificity of substrate selection not fully resolved
    • Whether speckle localization governs these substrates untested
  7. 2017 High

    SPOP's role in oncogenic transcription and immune evasion was consolidated through BET protein, c-MYC, and PD-L1 degradation, with CDK4-driven SPOP turnover linking the cell cycle to checkpoint ligand stability.

    Evidence Co-IP, in vivo ubiquitination, organoids, knockout mice, and CDK4/6 inhibitor and phosphorylation mapping

    PMID:28414305 PMID:28805820 PMID:28805822 PMID:29160310

    Open questions at the time
    • Relative substrate hierarchy in tumors not established
    • Did not quantify combined effect of simultaneous substrate stabilization
  8. 2017 High

    Non-degradative ubiquitination emerged as a distinct SPOP output, shown by INF2 modification that suppresses mitochondrial fission, extending SPOP beyond proteasomal targeting.

    Evidence Co-IP, ubiquitination assays, immunofluorescence, and mitochondrial fission assays with dominant-negative mutants

    PMID:28448495

    Open questions at the time
    • Chain linkage type not fully defined in this study
    • Downstream effectors of altered fission not mapped
  9. 2018 Medium

    SPOP was shown to control pluripotency and replication-stress responses, degrading Nanog under kinase control and promoting expression of DNA repair/replication factors via its interactome.

    Evidence Degron mutagenesis and ubiquitination (Nanog); proteomic interactome with DNA fiber and foci assays

    PMID:30124983 PMID:30595535 PMID:30595538

    Open questions at the time
    • Mechanism by which SPOP promotes repair-gene transcription not resolved
    • Direct versus indirect effects on replication factors unclear
  10. 2021 High

    ATM-triggered conformational activation of SPOP was structurally defined, explaining how DNA damage redirects SPOP to ubiquitinate 53BP1 (for p97-mediated chromatin extraction) and HIPK2 to favor homologous recombination.

    Evidence X-ray crystallography, phosphorylation mapping, ubiquitination assays, and cell-cycle/repair readouts

    PMID:34133717 PMID:34144977

    Open questions at the time
    • In vivo contribution to tumor repair phenotypes not fully quantified
    • Interplay between the 53BP1 and HIPK2 arms not resolved
  11. 2021 High

    The breadth of linkage-specific and non-degradative signaling was extended: K27-linked Geminin ubiquitination restrains re-replication, K27/K29 chains stabilize 17βHSD4 to limit androgen synthesis, and PDK1 and GLP degradation couple SPOP to AKT and DNA methylation.

    Evidence Linkage-specific ubiquitination, kinase assays, replication assays, methylome analysis, and CRISPR E3 screen with xenografts

    PMID:33762355 PMID:34353330 PMID:34588438 PMID:34599168

    Open questions at the time
    • Determinants selecting degradative versus non-degradative chains not generalized
    • Substrate-specific deubiquitinase counterparts mostly unidentified
  12. 2022 High

    SPOP was shown to regulate autophagy and antioxidant signaling through non-degradative ubiquitination of p62/SQSTM1, controlling its phase separation and Keap1-Nrf2 sequestration.

    Evidence Site-specific ubiquitination (K420), autophagy assays, and liquid-liquid phase separation experiments

    PMID:34987184

    Open questions at the time
    • Cytoplasmic versus nuclear SPOP pool governing p62 not fully delineated
    • Physiological autophagy thresholds in vivo not established
  13. 2023 High

    Oligomeric structure determination provided the structural rationale for non-MATH cancer mutations, linking endometrial cancer mutations to altered self-assembly interfaces.

    Evidence X-ray crystallography of oligomeric SPOP with mutational and biochemical validation

    PMID:36693379

    Open questions at the time
    • Functional consequences of altered assembly on specific substrates not exhaustively tested
    • Whether these mutants are gain- or loss-of-function context-dependent

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what determines, for any given substrate, whether SPOP deposits degradative versus non-degradative ubiquitin chains and how subnuclear partitioning, oligomerization state, and the spectrum of MATH-domain versus assembly-interface mutations integrate to specify substrate fate.
  • No unified model linking chain-type choice to substrate or localization
  • Quantitative substrate hierarchy across tissues unknown
  • Functional distinction between prostate (MATH) and endometrial (interface) mutations incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016874 ligase activity 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2 R-HSA-69306 DNA Replication 1 R-HSA-9612973 Autophagy 1
Partners
53BP1ARATMBRD4CUL3ERGP62/SQSTM1RBX1
Complex memberships
CUL3-RBX1 RING E3 ubiquitin ligase (CRL3-SPOP)

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 SPOP functions as a substrate adaptor for the CUL3-RING E3 ubiquitin ligase to ubiquitinate and target PD-L1 for proteasome-mediated degradation. Cyclin D-CDK4 phosphorylates SPOP, promoting SPOP's own degradation by the APC/C activator FZR1, thereby stabilizing PD-L1. Loss-of-function SPOP mutations compromise ubiquitination-mediated PD-L1 degradation. Co-immunoprecipitation, in vivo ubiquitination assays, pharmacological CDK4/6 inhibition, mouse tumor models, phosphorylation mapping Nature High 29160310
2017 CUL3-SPOP E3 ligase complex ubiquitinates BET proteins (BRD2, BRD3, BRD4) for proteasomal degradation. Prostate cancer-associated SPOP mutants fail to interact with BET proteins, leading to their accumulation and resistance to BET inhibitors. Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, prostate cancer organoids, Western blot of patient specimens Nature medicine High 28805820 28805822
2017 Wild-type SPOP recognizes a degron motif common among BET proteins and promotes their proteasomal degradation; prostate cancer SPOP mutants show impaired binding to BET proteins. BRD4 stabilization activates RAC1 and AKT-mTORC1 signaling as a consequence. Degron binding assay, ubiquitination assay, transcriptome and BRD4 cistrome analyses, prostate cancer cell lines and patient specimens Nature medicine High 28805822
2014 SPOP recognizes a Ser/Thr-rich degron in the hinge domain of full-length androgen receptor (AR) and induces its ubiquitination and proteasomal degradation, inhibiting AR-mediated transcription and prostate cancer cell growth. AR splice variants lacking the hinge domain escape SPOP-mediated degradation. Prostate cancer SPOP mutants cannot bind or promote AR destruction. Androgens antagonize SPOP-mediated AR degradation, whereas antiandrogens promote it. Co-immunoprecipitation, ubiquitination assays, degron mapping, siRNA knockdown, cell growth assays Cell reports High 24508459
2013 SPOP directly interacts with SRC-3 (NCOA3/AIB1) and promotes its CUL3-dependent ubiquitination and proteolysis, suppressing androgen receptor transcriptional activity. Prostate cancer-associated SPOP mutants cannot interact with SRC-3 or promote its ubiquitination and degradation. Co-immunoprecipitation, ubiquitination assays, proteasome inhibition, prostate cancer cell lines Proceedings of the National Academy of Sciences of the United States of America High 23559371
2015 SPOP recognizes ERG via the CUL3 ubiquitin ligase system and promotes ERG ubiquitination and proteasomal degradation. The SPOP/ERG interaction is modulated by CKI-mediated phosphorylation. Truncated ERG (ΔERG) encoded by the fusion gene evades SPOP-mediated destruction. Prostate cancer SPOP mutants are deficient in promoting ERG ubiquitination. DNA damage drugs (topoisomerase inhibitors) trigger CKI activation to restore SPOP/ΔERG interaction. Co-immunoprecipitation, ubiquitination assays, phosphorylation mapping, drug treatment experiments Molecular cell High 26344095
2016 SPOP self-associates into higher-order oligomers through BTB-mediated dimerization forming linear oligomers via BACK domain dimerization. Higher-order SPOP oligomerization is required for localization to liquid nuclear speckles; self-association-deficient SPOP mutants show diffuse nuclear distribution. Higher-order oligomerization stimulates CRL3(SPOP) ubiquitination efficiency for substrate Gli3, indicating nuclear speckles are hotspots of ubiquitination. Analytical ultracentrifugation, biophysical sizing, live-cell imaging, in vitro ubiquitination assays, domain mapping with mutants The EMBO journal High 27220849
2023 Cryo-EM/X-ray crystal structure of SPOP in its oligomeric form reveals new interfaces important for SPOP self-assembly. Many endometrial cancer mutations localize to newly identified oligomeric interfaces, providing the structural basis for their gain-of-function or altered-assembly cancer-causing properties. X-ray crystallography (oligomeric structure determination), mutagenesis, biochemical characterization of cancer mutants Molecular cell High 36693379
2021 ATM kinase phosphorylates SPOP in response to DNA damage, causing a conformational change (revealed by X-ray crystal structures) that stabilizes SPOP's interaction with 53BP1. SPOP then induces polyubiquitination of 53BP1, leading to 53BP1 extraction from chromatin by a p97/VCP segregase complex, promoting homologous recombination over NHEJ during S phase. Cancer-derived SPOP mutations block SPOP interaction with 53BP1, inducing HR defects. X-ray crystallography, in vivo and in vitro ubiquitination assays, Co-immunoprecipitation, phosphorylation mapping, cell cycle analysis Science advances High 34144977
2015 SPOP mutations are associated with genomic instability in prostate cancer. SPOP mutation results in a transcriptional response consistent with BRCA1 inactivation, impairing homology-directed repair (HDR) of DNA double-strand breaks. SPOP mutation sensitizes cells to PARP inhibitors. Epistasis/transcriptional profiling, DNA repair functional assays, in vivo mouse models, PARP inhibitor sensitivity assay eLife Medium 26374986
2021 SPOP promotes K27-linked non-degradative polyubiquitination of Geminin at K100 and K127, preventing DNA replication over-firing by blocking Cdt1 association with the MCM complex. Cancer-associated SPOP mutations impair Geminin K27-linked polyubiquitination and induce replication origin over-firing and re-replication. Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, ubiquitin chain linkage analysis, DNA replication assays, cancer mutant analysis Nature communications High 34599168
2016 SPOP is critically involved in SETD2 protein stability control; the SPOP/CUL3 complex is responsible for SETD2 polyubiquitination both in vivo and in vitro. Modulation of SPOP expression confers differential H3K36me3 levels on SETD2 target genes and induces H3K36me3-coupled alternative splicing events. Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, ChIP-Seq, RNA splicing analysis Nucleic acids research High 27614073
2017 SPOP recognizes INF2 via a Ser/Thr-rich motif in its C-terminal region and triggers atypical (non-degradative) polyubiquitination. This modification reduces INF2 localization in the ER and mitochondrially associated DRP1 puncta, impairing INF2-mediated mitochondrial fission. Prostate cancer SPOP mutants increase INF2 ER localization and promote mitochondrial fission via dominant-negative effect. Co-immunoprecipitation, ubiquitination assays, immunofluorescence, mitochondrial fission assays, dominant-negative mutant analysis PLoS genetics High 28448495
2018 SPOP physically interacts with Nanog via a conserved degron motif and promotes Nanog poly-ubiquitination and subsequent proteasomal degradation. Cancer-derived mutations in SPOP or at the Nanog degron (S68Y) disrupt this destruction. Pin1 oncoprotein acts as an upstream regulator that impairs Nanog recognition by SPOP, stabilizing Nanog. Co-immunoprecipitation, ubiquitination assays, degron mutagenesis, cancer mutant analysis, Pin1 interaction studies Developmental cell High 30595535 30595538
2018 AMPK-BRAF signaling controls SPOP-mediated NANOG degradation through phosphorylation of NANOG at Ser68, which blocks the SPOP-NANOG interaction. Cancer-associated mutations of SPOP or the NANOG S68Y mutation abrogates SPOP-mediated degradation. Co-immunoprecipitation, ubiquitination assays, phosphorylation mapping, kinase assays Developmental cell Medium 30595535
2021 SPOP promotes ubiquitination and degradation of PDK1 in a CK1/GSK3β-mediated phosphorylation-dependent manner, by directly binding a degron in PDK1. This suppresses AKT kinase activity. Prostate cancer SPOP mutations impair PDK1 degradation and activate AKT. CRISPR-based E3 ligase screen, Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, in vitro kinase assays, mass spectrometry, xenograft models Molecular cancer High 34353330
2017 SPOP physically interacts with c-MYC protein and promotes c-MYC ubiquitination and degradation. PC-associated SPOP mutants or SPOP knockdown increase c-MYC protein levels. Prostate-specific biallelic Spop knockout mice develop prostatic intraepithelial neoplasia with elevated c-MYC. Co-immunoprecipitation, ubiquitination assays, prostate-specific knockout mouse model, gene expression analysis Oncogene High 28414305
2015 SPOP recognizes multiple Ser/Thr-rich degrons in the AF2 domain of estrogen receptor-α (ERα) and triggers ERα ubiquitin-proteasome pathway degradation as part of the SPOP-CUL3-RBX1 E3 complex. SPOP participates in estrogen-induced ERα degradation. Endometrial cancer SPOP mutants are defective in promoting ERα ubiquitination and degradation. Co-immunoprecipitation, in vivo and in vitro ubiquitination assays, degron mapping, siRNA knockdown, endometrial cancer mutant analysis Cell death & disease High 25766326
2022 Cytoplasmic SPOP binds p62/SQSTM1 and induces non-degradative ubiquitination of p62 at residue K420 within the UBA domain. This modification decreases p62 puncta formation, liquid phase condensation, dimerization, and ubiquitin-binding capacity, suppressing p62-dependent autophagy. SPOP also relieves p62-mediated Keap1 sequestration, reducing Nrf2-mediated antioxidant transcription. Prostate cancer SPOP mutants fail to ubiquitinate p62 and promote autophagy and Nrf2 activation in a dominant-negative manner. Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, site-specific mutagenesis, autophagy assays, liquid-liquid phase separation experiments Cell death and differentiation High 34987184
2021 SPOP binds and promotes polyubiquitination and proteasomal degradation of the histone methyltransferase GLP, and by extension its partner G9a. SPOP mutation induces GLP/G9a stabilization, aberrant global DNA hypermethylation in prostate cancer cells, and silencing of tumor suppressor genes (FOXO3, GATA5, NDRG1). Co-immunoprecipitation, ubiquitination assays, genome-wide DNA methylome analysis, gene expression analysis, cancer mutant validation Nature communications High 34588438
2018 TRIM28 interacts with TRIM24 (a known SPOP substrate) to prevent its ubiquitination and degradation by SPOP, acting as a competitive upstream regulator. TRIM28 facilitates TRIM24 chromatin occupancy and augments AR signaling. Co-immunoprecipitation, ubiquitination assays, chromatin immunoprecipitation, xenograft studies Nature communications Medium 30479348
2019 SPOP recognizes and triggers ubiquitin-dependent proteasomal degradation of Caprin1 (a stress granule nucleating protein). Prostate cancer SPOP mutants fail to degrade Caprin1, leading to elevated Caprin1 and enhanced stress granule assembly, conferring resistance to docetaxel and other stress inducers. Yeast two-hybrid screen, Co-immunoprecipitation, ubiquitination assays, stress granule assays, xenograft models, patient specimen analysis Molecular cancer Medium 31771591
2016 In mouse models, Spop directly targets the Gli3 repressor for ubiquitination and degradation, positively regulating Indian Hedgehog (Ihh) signaling and skeletal development. Loss of Spop results in upregulation of full-length and repressor forms of Gli3, down-regulation of Ihh target genes (Ptch1, Pthlh), and skeletal defects rescued by reducing Gli3 dosage. Spop null mouse model, conditional mouse model, genetic epistasis (reducing Gli3 dosage), in vivo ubiquitination assays Proceedings of the National Academy of Sciences of the United States of America High 27930311
2014 SPOP is recruited to DNA double-strand break sites, forms nuclear foci co-localizing with γ-H2AX foci, and interacts with ATM kinase in response to DNA damage. SPOP recruitment is predominantly dependent on ATM kinase activity. SPOP knockdown results in impaired DNA damage response and hypersensitivity to ionizing irradiation. Immunofluorescence (foci formation), Co-immunoprecipitation, siRNA knockdown, ionizing radiation sensitivity assays Carcinogenesis Medium 24451148
2022 SPOP negatively regulates PD-L1 expression at the transcriptional level by binding to IRF1 (a transcription factor for PD-L1) and triggering its ubiquitin-proteasomal degradation. Endometrial cancer SPOP mutants lose capacity to degrade IRF1, instead stabilizing it and upregulating PD-L1 expression. Co-immunoprecipitation, ubiquitination assays, luciferase reporter assays, xenograft tumor models Cell death and differentiation Medium 36481790
2021 SPOP promotes ATF2 ubiquitination and degradation via recognition of multiple Ser/Thr-rich degrons in ATF2 by the SPOP-CUL3-RBX1 complex. Prostate cancer SPOP mutants are defective in promoting ATF2 degradation. Yeast two-hybrid screen, Co-immunoprecipitation, ubiquitination assays, degron mapping, Transwell migration and invasion assays Journal of experimental & clinical cancer research : CR Medium 29996942
2016 SPOP interacts with Cdc20 and promotes its poly-ubiquitination and subsequent proteasomal degradation in a degron-dependent manner via CUL3. Prostate cancer-derived SPOP mutants fail to interact with Cdc20 to promote its degradation. Co-immunoprecipitation, ubiquitination assays, pharmacological CUL inhibition (MLN4924), half-life assays Cancer letters Medium 27780719
2018 SPOP directly interacts with CYCLIN E1 and regulates its stability through poly-ubiquitination by the SPOP/CUL3/RBX1 complex. CDK2 competes with SPOP for CYCLIN E1 interaction, suggesting SPOP preferentially targets CDK2-free CYCLIN E1. Loss of CYCLIN E1 regulation by SPOP contributes to prostate cancer cell proliferation. Co-immunoprecipitation, ubiquitination assays, competition binding assays, prostate cancer cell lines Cell death and differentiation Medium 30237511
2014 SPOP recognizes a Ser/Thr-rich degron in the transactivation domain of DDIT3/CHOP and triggers its degradation via the ubiquitin-proteasome pathway through the SPOP-CUL3-RBX1 complex. Prostate cancer SPOP mutants are defective in promoting DDIT3 degradation. Co-immunoprecipitation, ubiquitination assays, degron mapping, prostate cancer mutant analysis Human mutation Medium 24990631
2021 SPOP is phosphorylated at Ser119 by ATM kinase upon DNA damage, enhancing SPOP binding to HIPK2. SPOP induces non-degradative ubiquitination of HIPK2, which increases HIPK2 phosphorylation of HP1γ and promotes HP1γ dissociation from H3K9me3 to initiate DNA damage repair. Prostate cancer SPOP mutations abrogate this SPOP-HIPK2 axis. Co-immunoprecipitation, ubiquitination assays, phosphorylation mapping, DNA damage repair assays, cancer mutant analysis Nucleic acids research Medium 34133717
2019 ILF3 is a substrate of SPOP; EGF-MEK-ERK pathway-mediated phosphorylation of ILF3 hinders SPOP-mediated poly-ubiquitination and degradation of ILF3. ILF3 regulates the SGOC (Serine-Glycine-One-Carbon) metabolic pathway by regulating SGOC gene mRNA stability. Co-immunoprecipitation, ubiquitination assays, phosphorylation mapping, patient-derived xenografts Cell research Medium 31772275
2022 CUL3-SPOP E3 ligase promotes ASCT2/SLC1A5 (glutamine transporter) ubiquitylation and degradation, controlling glutamine uptake. MLN4924 (neddylation inhibitor) inactivates CRL3-SPOP, causing ASCT2 accumulation. SPOP itself undergoes auto-ubiquitylation upon glutamine deprivation. Co-immunoprecipitation, ubiquitination assays, pharmacological neddylation inhibition, siRNA knockdown, breast cancer specimens Nature communications Medium 35641493
2021 SPOP binds and promotes non-degradative K27- and K29-linked polyubiquitination of 17βHSD4 at a functional SBC motif (315RATST319). This stabilizes 17βHSD4. SGK3-mediated phosphorylation of S318 in the SBC blocks SPOP binding and instead leads to SKP2-dependent K48-linked degradative ubiquitination of 17βHSD4. Prostate cancer SPOP mutations impair SPOP-17βHSD4 interaction, causing 17βHSD4 destruction and increased testosterone production. Co-immunoprecipitation, in vivo and in vitro ubiquitination assays (linkage-specific), kinase assays, xenograft mouse models, patient specimens Cancer research High 33762355
2016 SPOP promotes DAXX ubiquitination and degradation as part of a CUL3-SPOP-DAXX axis in vascular endothelial cells. DAXX degradation by SPOP is required for VEGFR2 mRNA expression. Knockdown of SPOP or CUL3 upregulates DAXX protein and downregulates VEGFR2 levels. Simultaneous knockdown of SPOP and DAXX reverses VEGFR2 downregulation. siRNA knockdown, Western blotting, epistasis by double-knockdown, endothelial cell functional assays Scientific reports Medium 28216678
2021 SPOP targets and destabilizes STING1 protein. Prostate cancer-associated SPOP mutations result in upregulated non-canonical STING-NF-κB signaling. PARP inhibitor treatment shifts this signaling from immunosuppressive non-canonical STING-NF-κB to antitumor canonical cGAS-STING-IFNβ signaling in SPOP-mutant prostate cancer. Proteomics analysis, genetically modified cell line models, in vitro and in vivo PARP inhibitor treatment, transcriptomic analysis Clinical cancer research Medium 37581614
2020 SPOP negatively regulates TLR-induced inflammation by disrupting MyD88 self-association. SPOP is recruited to MyD88 following TLR4 activation and translocates from the nucleus to the cytoplasm upon TLR4 activation. SPOP depletion promotes MyD88 aggregation and recruitment of downstream signaling kinases IRAK4, IRAK1, and IRAK2. Co-immunoprecipitation, SPOP overexpression and knockdown, immunofluorescence (subcellular localization), NF-κB reporter assays Cellular & molecular immunology Medium 32235916
2020 SPOP promotes ubiquitination and proteasomal degradation of MyD88 via recognizing the intermediate domain of MyD88. Knockdown or genetic ablation of SPOP leads to aberrant elevation of MyD88 protein. SPOP negatively regulates NF-κB pathway activity and IL-1β production upon LPS challenge. Spop-deficient mice are more susceptible to Salmonella typhimurium infection. Co-immunoprecipitation, ubiquitination assays, Spop-knockout mice, infection model PLoS pathogens Medium 32365080
2021 SPOP promotes ubiquitination and degradation of LATS1 (a Hippo pathway tumor suppressor) via a degron-dependent interaction with CUL3. SPOP overexpression promotes kidney cancer cell proliferation and invasion partly through LATS1 degradation. Co-immunoprecipitation, ubiquitination assays, protein half-life assays, xenograft models EBioMedicine Medium 32460168
2021 SPOP promotes CDCA5 poly-ubiquitination and proteasomal degradation in a degron-dependent manner. Prostate cancer SPOP mutations impair this effect. CDCA5 depletion leads to G2M arrest, sister chromatid cohesion defects, and apoptosis via the AKT pathway. Co-immunoprecipitation, ubiquitination assays, cell cycle analysis, functional knockdown assays Neoplasia (New York, N.Y.) Medium 34509929
2017 SPOP mutation activates both PI3K/mTOR and androgen receptor signaling in prostate cancer in vivo, effectively uncoupling the normal negative feedback between these two pathways, as demonstrated in a conditional mutant SPOP mouse model with Pten loss. Conditional mouse model (prostate-specific mutant SPOP expression), prostate organoids, human prostate cancer sample analysis, transcriptional profiling Cancer cell Medium 28292441
2020 AURORA A (AURKA) kinase directly phosphorylates SPOP at three sites, causing SPOP ubiquitylation and degradation. Conversely, SPOP degrades AURKA via a feedback loop. SPOP degradation by AURKA stabilizes AR, ARv7, and c-Myc, promoting oncogenic phenotypes. Phospho-resistant SPOP fully abrogates tumorigenesis in vivo. In vitro kinase assay (direct phosphorylation), ubiquitination assays, Co-immunoprecipitation, xenograft studies Cancers Medium 33158056
2020 LIMK2 kinase directly phosphorylates SPOP at three sites, causing SPOP degradation. SPOP promotes LIMK2 ubiquitylation, creating a feedback loop. Phospho-resistant SPOP completely suppresses tumorigenesis in vivo. In vitro kinase assay, ubiquitination assays, Co-immunoprecipitation, xenograft studies British journal of cancer Medium 33311589
2021 ERG upregulates wild-type SPOP to dampen AR signaling and sustain ERG activity through SPOP-mediated degradation of the bromodomain histone reader ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG function and enable oncogenic AR signaling. This antagonism makes SPOP-mutant and ERG tumors synthetic sick. Co-immunoprecipitation, ubiquitination assays, transcriptomic analysis, genetic epistasis in prostate cancer models Nature communications Medium 33531470
2021 G3BP1 interacts with SPOP and functions as a competitive inhibitor of CUL3-SPOP E3 ligase activity, providing a mechanism to inactivate SPOP tumor suppressor function without SPOP mutation in prostate cancer. AR directly upregulates G3BP1 transcription, creating a feed-forward amplification loop. Co-immunoprecipitation, transcriptomic analysis, functional knockdown assays, AR ChIP analysis Nature communications Medium 34795264
2019 SPOP controls fetal hemoglobin (HbF) expression in adult erythroid cells as a CUL3-RING ligase adaptor. SPOP depletion or dominant-negative SPOP overexpression significantly raises fetal globin mRNA and protein levels, independently of BCL11A and LRF HbF repressors. CRISPR-Cas9 library screen, siRNA knockdown, dominant-negative overexpression, transcriptome and proteome analyses Blood advances Medium 31126914
2021 Intrinsically disordered substrates dictate SPOP subnuclear localization. Pdx1, which has only moderate valency (two SPOP-binding motifs), does not phase separate with SPOP and instead prompts SPOP relocalization from nuclear speckles to the diffuse nucleoplasm. SPOP-mediated ubiquitination of Pdx1 occurs in the nucleoplasm, and both SB motifs are required for efficient Pdx1 turnover. NMR spectroscopy (SB motif identification), live-cell imaging (SPOP relocalization), ubiquitination assays The Journal of biological chemistry Medium 33894201
2018 SPOP promotes transcriptional expression of DNA repair and replication factors including BRCA2, ATR, CHK1, and RAD51. SPOP knockdown leads to spontaneous replication stress, impaired RAD51 foci formation, impaired CHK1 activation, and compromised recovery from replication fork stalling. SPOP interactome analysis shows wild-type SPOP (but not mutant SPOP) associates with transcription, mRNA splicing and export complexes. Proteomic interactome analysis, siRNA knockdown, RAD51/CHK1 foci formation, DNA fiber assays, gene expression analysis Nucleic acids research Medium 30124983
2021 SPOP promotes SIRT2 binding and degradation by the 26S proteasome. SPOP loss or mutations impair SIRT2 degradation in non-small cell lung cancer cells. Co-immunoprecipitation, proteasome inhibition assays, Western blot in cancer cell lines Biochemical and biophysical research communications Low 28073696
2002 SPOP (Spop) physically interacts with macroH2A1.2 histone variant via its MATH domain, which binds the putative leucine zipper domain of macroH2A1.2. This was identified by yeast two-hybrid and confirmed by GST pull-down. Yeast two-hybrid screen, GST pull-down, domain mapping Biochimica et biophysica acta Low 12183056
2023 SPOP promotes ubiquitination and degradation of EWS-FLI1 fusion oncoprotein in Ewing sarcoma. Casein kinase 1-mediated phosphorylation of the VTSSS degron in the FLI1 domain enhances SPOP-mediated EWS-FLI1 degradation. OTUD7A deubiquitinase opposes SPOP by deubiquitinating and stabilizing EWS-FLI1. Co-immunoprecipitation, ubiquitination assays, phosphorylation mapping, Ewing sarcoma cell line knockdown, xenograft mouse models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 34060252
2019 SPOP recognizes and promotes ubiquitination and degradation of ZBTB3 transcription factor via two Ser/Thr-rich degrons by the SPOP-CUL3-RBX1 E3 complex. Endometrial cancer SPOP mutants are defective in regulating ZBTB3 stability. SPOP inactivation promotes endometrial cell proliferation via ZBTB3-dependent SHH upregulation. Co-immunoprecipitation, ubiquitination assays, degron mapping, luciferase reporter assays, cancer mutant analysis American journal of cancer research Medium 31911863
2021 SPOP promotes ubiquitination and degradation of HMGCS1 (HMG-CoA synthase 1), and CSN6 antagonizes SPOP to stabilize HMGCS1. HMGCS1 stabilization activates YAP1 to promote hepatocellular carcinoma growth. Co-immunoprecipitation, ubiquitination assays, xenograft and orthotopic liver cancer models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38308184
2020 SPOP promotes SPOP-mediated ubiquitination and degradation of PTEN in kidney cancer when SPOP is mislocalized to the cytoplasm. Small molecule inhibitors of the SPOP-substrate protein interaction increase PTEN levels, decrease PTEN ubiquitination, and reduce phosphorylated AKT and ERK in ccRCC cell lines. Structure-based small molecule design, in vitro binding assays, Co-immunoprecipitation, ubiquitination assays, cell viability assays Journal of medicinal chemistry Medium 32297747
2020 O-GlcNAcylation of SPOP at Ser96 by OGT increases nuclear positioning of SPOP in hepatoma cells, alleviating SPOP-mediated ubiquitination of the Nogo-B/RTN4B oncoprotein and thereby promoting HCC progression. In normal liver cells, cytoplasmic SPOP ubiquitinates Nogo-B via N-terminal SBC motifs. Abolition of O-GlcNAcylation by S96A mutation increased cytoplasmic SPOP localization. Co-immunoprecipitation, ubiquitination assays, subcellular fractionation, site-specific mutagenesis, in vitro and in vivo cancer models Oncogene Medium 36604567
2020 SPOP was identified as a novel substrate of STAT3 in bladder cancer; SPOP deficiency increases STAT3 protein stability, leading to elevated CCL2 secretion and macrophage M2 polarization. VEZF1 directly activates SPOP transcription, and its overexpression suppresses STAT3/CCL2/IL-6 axis effects. Co-immunoprecipitation, in vitro ubiquitination assay, luciferase reporter, ChIP assay, co-culture system Theranostics Medium 39479456

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 857 29160310
2017 Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Nature medicine 285 28805820
2017 Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nature medicine 253 28805822
2014 Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell reports 232 24508459
2013 Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover. Proceedings of the National Academy of Sciences of the United States of America 207 23559371
2015 SPOP Promotes Ubiquitination and Degradation of the ERG Oncoprotein to Suppress Prostate Cancer Progression. Molecular cell 181 26344095
2016 Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles. The EMBO journal 178 27220849
2017 SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer cell 167 28292441
2015 SPOP mutation leads to genomic instability in prostate cancer. eLife 158 26374986
2014 SPOP mutations in prostate cancer across demographically diverse patient cohorts. Neoplasia (New York, N.Y.) 132 24563616
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 117 34168048
2019 Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly. Molecular cancer 107 31771591
2017 SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein. Oncogene 103 28414305
2018 TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression. Nature communications 100 30479348
2019 ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer. Cell research 92 31772275
2020 The emerging role of SPOP protein in tumorigenesis and cancer therapy. Molecular cancer 91 31901237
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 80 34987184
2020 SPOP and cancer: a systematic review. American journal of cancer research 79 32266086
2016 Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer. Cancer cell 77 27622336
2018 AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness. Developmental cell 76 30595535
2014 The emerging role of speckle-type POZ protein (SPOP) in cancer development. Drug discovery today 75 25058385
2021 SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions. Molecular cancer 72 34353330
2022 Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer cells. Nature communications 68 35641493
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 65 36088616
2016 SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. Nucleic acids research 65 27614073
2017 Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer. PLoS genetics 64 28448495
2014 SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer. Journal of experimental & clinical cancer research : CR 64 25204354
2018 SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression. Developmental cell 63 30595538
2019 The ubiquitin ligase adaptor SPOP in cancer. The FEBS journal 61 31495053
2015 Endometrial cancer-associated mutants of SPOP are defective in regulating estrogen receptor-α protein turnover. Cell death & disease 61 25766326
2021 SPOP and OTUD7A Control EWS-FLI1 Protein Stability to Govern Ewing Sarcoma Growth. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 60 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 57 36512624
2022 SPOP mutations promote tumor immune escape in endometrial cancer via the IRF1-PD-L1 axis. Cell death and differentiation 51 36481790
2018 SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression. Journal of experimental & clinical cancer research : CR 50 29996942
2021 ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication. Science advances 49 34144977
2018 SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability. Cell death and differentiation 48 30237511
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 45 34783071
2020 SPOP negatively regulates Toll-like receptor-induced inflammation by disrupting MyD88 self-association. Cellular & molecular immunology 43 32235916
2014 Speckle-type POZ protein, SPOP, is involved in the DNA damage response. Carcinogenesis 43 24451148
2016 SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma. International journal of oncology 42 27572476
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
2021 SPOP mutation induces DNA methylation via stabilizing GLP/G9a. Nature communications 40 34588438
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
2019 Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals. Nature communications 35 31604927
2018 SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability. Nucleic acids research 35 30124983
2018 The E2F1-miR-520/372/373-SPOP Axis Modulates Progression of Renal Carcinoma. Cancer research 35 30348808
2024 CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 38308184
2021 Mutated SPOP E3 Ligase Promotes 17βHSD4 Protein Degradation to Drive Androgenesis and Prostate Cancer Progression. Cancer research 32 33762355
2021 SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition. Nature communications 32 34599168
2021 G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer. Nature communications 32 34795264
2019 GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis. Cell reports 32 31167144
2017 SPOP promotes SIRT2 degradation and suppresses non-small cell lung cancer cell growth. Biochemical and biophysical research communications 32 28073696
2023 Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation. Molecular cell 31 36693379
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
2024 BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma. Cellular and molecular life sciences : CMLS 29 38340178
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
2019 SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG. Cell death & disease 29 31624231
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
2017 SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG. The Journal of clinical investigation 28 29202479
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 27 35364375
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 26 39479456
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
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 25 37581614
2019 The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells. Blood advances 25 31126914
2022 Enhanced autophagy and NFE2L2/NRF2 pathway activation in SPOP mutation-driven prostate cancer. Autophagy 24 35438056
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
2023 O-GlcNAcylation of SPOP promotes carcinogenesis in hepatocellular carcinoma. Oncogene 23 36604567
2019 SPOP regulates the DNA damage response and lung adenocarcinoma cell response to radiation. American journal of cancer research 23 31392082
2020 Structure-Activity Relationship of SPOP Inhibitors against Kidney Cancer. Journal of medicinal chemistry 21 32297747
2021 Intrinsically disordered substrates dictate SPOP subnuclear localization and ubiquitination activity. The Journal of biological chemistry 20 33894201
2021 SPOP and CUL3 Modulate the Sonic Hedgehog Signal Response Through Controlled Degradation of GLI Family Transcription Factors. Frontiers in cell and developmental biology 20 34395437
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 SPOP-mutant prostate cancer: Translating fundamental biology into patient care. Cancer letters 19 34974131
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
2020 TGF-β signaling regulates SPOP expression and promotes prostate cancer cell stemness. Aging 18 32364525
2024 Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39499771
2022 The speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing TWIST1. Cell death discovery 17 36115849
2020 The GPER1/SPOP axis mediates ubiquitination-dependent degradation of ERα to inhibit the growth of breast cancer induced by oestrogen. Cancer letters 17 33069770
2020 S119N Mutation of the E3 Ubiquitin Ligase SPOP Suppresses SLC7A1 Degradation to Regulate Hepatoblastoma Progression. Molecular therapy oncolytics 17 33209975
2019 SPOP and FOXA1 mutations are associated with PSA recurrence in ERG wt tumors, and SPOP downregulation with ERG-rearranged prostate cancer. The Prostate 17 31090082
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
2023 Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer. European urology oncology 16 38072760
2022 Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer. Frontiers in oncology 16 36119488
2020 SPOP is essential for DNA-protein cross-link repair in prostate cancer cells: SPOP-dependent removal of topoisomerase 2A from the topoisomerase 2A-DNA cleavage complex. Molecular biology of the cell 16 31967940
2020 De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders. American journal of human genetics 16 32109420
2020 The Roles of SPOP in DNA Damage Response and DNA Replication. International journal of molecular sciences 15 33023230

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