ArticleCell reports2014
Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 1 of them a synthesis that pooled it.
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Who cites it
196 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients: A meta-analysis.Medicine · 2019Pooled it
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- Article
- SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.Nature communications · 2026Article
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis.Nature communications · 2026Article
- Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs).Gene · 2026Review
- MYC contributes to targeted therapy resistance in lung cancers driven by MET exon 14-skipping alteration.NPJ precision oncology · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- TRIM24-mediated K27-linked ubiquitination of ULK1 alleviates energy stress-induced autophagy and promote prostate cancer growth in the context of SPOP mutation.Cell death and differentiation · 2026Article
- Outcomes for Patients With SPOP Mutated Castration-Resistant Prostate Cancer (CRPC) Treated With an Androgen Receptor Pathway Inhibitor (ARPI).Clinical genitourinary cancer · 2026Article
- The Clinical Significance of SPOP Upregulation and Nuclear Accumulation in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Androgen Signaling Represses Homeobox C9, an Inhibitor of Androgen Receptor, in Prostate Cancer Cells.International journal of molecular sciences · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Systematic Characterization of Cancer-Associated SPOP Mutants Reveals Novel and Reprogrammable Degradative Activities.Chembiochem : a European journal of chemical biology · 2026Article
- Cancer degronopathies and protein-fate biomarkers in drug resistance and cancer progression: signalling mechanisms, measurement and translational limits.Frontiers in cell and developmental biology · 2026Review
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- SPOP mediates apoptosis and protects against necroptosis by regulating ubiquitination of RIPK1 and RIPK3.JCI insight · 2025Article
- Parp7 generates an ADP-ribosyl degron that controls negative feedback of androgen signaling.The EMBO journal · 2025Article
136 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The SPOP E3 ubiquitin ligase gene is frequently mutated in human prostate cancers. Here, we demonstrate that SPOP recognizes a Ser/Thr-rich degron in the hinge domain of androgen receptor (AR) and induces degradation of full-length AR and inhibition of AR-mediated gene transcription and prostate cancer cell growth. AR splicing variants, most of which lack the hinge domain, escape SPOP-mediated degradation. Prostate-cancer-associated mutants of SPOP cannot bind to and promote AR destruction. Furthermore, androgens antagonize SPOP-mediated degradation of AR, whereas antiandrogens promote this process. This study identifies AR as a bona fide substrate of SPOP and elucidates a role of SPOP mutations in prostate cancer, thus implying the importance of this pathway in resistance to antiandrogen therapy of prostate cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.