ArticleThe Journal of biological chemistry2012
Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 131 citations in OpenAlex.
- Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.Cancer research communications · 2026Article
- A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding.Science advances · 2026Article
- Targeting PCNA in Cancer: A Paradigm Shift from Static Inhibition to Dynamic Network Modulation.Oncology research · 2026Review
- Article
- AOH1996, an Inhibitor of PCNA, Sensitises Breast Cancer Cells to Cytotoxic Chemotherapy.Breast cancer (Dove Medical Press) · 2026Article
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Versatile enhancement of the killing potential of anti-cancer agents achieved by peptide mimetics of the PCNA interface towards specialized DNA polymerases.Cell death & disease · 2025Article
- Lysine Acetyltransferase 8: A Target for Natural Compounds in Cancer Therapy.International journal of molecular sciences · 2025Review
- Neutrophils Display Novel Partners of Cytosolic Proliferating Cell Nuclear Antigen Involved in Interferon Response in COVID-19 Patients.Journal of innate immunity · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Beginning at the ends: telomere and telomere-based cancer therapeutics.Molecular genetics and genomics : MGG · 2024Review
- Review
- Identification of a potent PCNA-p15-interaction inhibitor by autodisplay-based peptide library screening.Microbial biotechnology · 2024Article
- Bavachinin protects the liver in NAFLD by promoting regeneration via targeting PCNA.Journal of advanced research · 2024Article
- The potential of PCNA inhibition as a therapeutic strategy in cervical cancer.Journal of medical virology · 2023Review
- Structural and functional studies of PCNA from African swine fever virus.Journal of virology · 2023Article
- A FRET-Based Assay for the Identification of PCNA Inhibitors.International journal of molecular sciences · 2023Article
- Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.PLoS pathogens · 2023Article
- Review
- Article
12 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
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have discovered that 3,3',5-triiodothyronine (T3) inhibits binding of a PIP-box sequence peptide to proliferating cell nuclear antigen (PCNA) protein by competing for the same binding site, as evidenced by the co-crystal structure of the PCNA-T3 complex at 2.1 Å resolution. Based on this observation, we have designed a novel, non-peptide small molecule PCNA inhibitor, T2 amino alcohol (T2AA), a T3 derivative that lacks thyroid hormone activity. T2AA inhibited interaction of PCNA/PIP-box peptide with an IC(50) of ~1 μm and also PCNA and full-length p21 protein, the tightest PCNA ligand protein known to date. T2AA abolished interaction of PCNA and DNA polymerase δ in cellular chromatin. De novo DNA synthesis was inhibited by T2AA, and the cells were arrested in S-phase. T2AA inhibited growth of cancer cells with induction of early apoptosis. Concurrently, Chk1 and RPA32 in the chromatin are phosphorylated, suggesting that T2AA causes DNA replication stress by stalling DNA replication forks. T2AA significantly inhibited translesion DNA synthesis on a cisplatin-cross-linked template in cells. When cells were treated with a combination of cisplatin and T2AA, a significant increase in phospho(Ser(139))histone H2AX induction and cell growth inhibition was observed.
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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.