ArticleNature communications2021
SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Homologous recombination deficiency and genomic alterations in advanced prostate cancer: insights for precision therapy.The oncologist · 2026Article
- Ubiquitin System-Driven Proteostasis in DNA Damage Response.International journal of molecular sciences · 2026Review
- Graph neural network-based risk stratification of prostate cancer using gene expression and SHAP interpretability.PloS one · 2026Article
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- KBTBD11 loss promotes AKT hyperactivation and therapeutic vulnerability in prostate cancer.Oncogene · 2025Article
- Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.The Journal of clinical investigation · 2025Article
- DNA2 protein destruction dictates DNA hyperexcision, cGAS-STING activation, and innate immune response in CDK12-deregulated cancers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
- SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer.JCI insight · 2025Article
- Cul3 substrate adaptor SPOP targets Nup153 for degradation.Molecular biology of the cell · 2025Article
- Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- BAY11-7082 Targets RNF25 to Reverse TRIP4 Ubiquitination-dependent NF-κB Activation and Apoptosis Resistance in Renal Cell Carcinoma.International journal of biological sciences · 2025Article
- DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity.Nature communications · 2024Article
- Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.European urology oncology · 2024Article
- CK2-dependent degradation of CBX3 dictates replication fork stalling and PARP inhibitor sensitivity.Science advances · 2024Article
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation.Nature communications · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.
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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.