ArticleNature2014
Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
- Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.Frontiers in oncology · 2022Pooled it
- The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML.Journal of translational medicine · 2021Trial
- Condensin I but not Condensin II is crucial for mitotic chromosome mechanics.Nature communications · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Computational proteome-wide screening reveals potential targets of astragaloside IV inFrontiers in veterinary science · 2026Article
- Multimodal integration of pathomics and single-cell transcriptomics reveals CDC20 as a link between prostate cancer recurrence and benzo[a]pyrene-responsive phenotypes.Frontiers in cell and developmental biology · 2026Article
- Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex.bioRxiv : the preprint server for biology · 2025Article
- The Critical Role of Enhanced OXPHOS and Mitochondrial Hyperpolarization in Simulated Microgravity-Induced Oocyte Maturation Arrest.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Ubiquitin-dependent proteolysis of KNL2 driven by APC/CCDC20 is critical for centromere integrity and mitotic fidelity.The Plant cell · 2025Article
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- Article
- A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.Journal of medicinal chemistry · 2025Article
- Evaluating the multitargeted potency of Pixuvri against cell cycle regulation proteins in cervical cancer.Frontiers in oncology · 2025Article
- The Use of APC/C Antagonists to Promote Mitotic Catastrophe in Cancer Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Targeting APC/C Ubiquitin E3-Ligase Activation with Pyrimidinethylcarbamate Apcin Analogues for the Treatment of Breast Cancer.Biomolecules · 2024Article
- Spatial control of the APC/C ensures the rapid degradation of cyclin B1.The EMBO journal · 2024Article
- Suppressing Anaphase-Promoting Complex/Cyclosome-Cell Division Cycle 20 Activity to Enhance the Effectiveness of Anti-Cancer Drugs That Induce Multipolar Mitotic Spindles.International journal of molecular sciences · 2024Review
99 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-l-arginine methyl ester, a small molecule that blocks the APC/C-Cdc20 interaction. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine.
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What OpenQuestion holds
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.