ArticleJournal of biomolecular screening2013
High-throughput screening AlphaScreen assay for identification of small-molecule inhibitors of ubiquitin E3 ligase SCFSkp2-Cks1.
Article in Journal of biomolecular screening, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- Structure-Based Discovery of Fumiquinazolines as Skp2-Cks1 Protein-Protein Interaction Disruptors: Mechanistic Computational Insights and Experimental Validation.ChemMedChem · 2026Article
- Structure-based discovery of diphenylpyrazines as disruptors of the Skp2-Cks1 protein-protein interaction: computational insights and biochemical validation.Journal of computer-aided molecular design · 2026Article
- Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.The Journal of clinical investigation · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- TRIM33 Is a Co-Regulator of Estrogen Receptor Alpha.Cancers · 2024Article
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.Communications biology · 2023Article
- Review
- A series of xanthenes inhibiting Rad6 function and Rad6-Rad18 interaction in the PCNA ubiquitination cascade.iScience · 2022Article
- Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1.Scientific reports · 2021Article
- Review
- Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy.Frontiers in oncology · 2021Review
- The Skp2 Pathway: A Critical Target for Cancer Therapy.Seminars in cancer biology · 2020Review
- [Targeting Cullin-RING E3 ligases for anti-cancer therapy: efforts on drug discovery].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- F-Box Proteins and Cancer.Cancers · 2020Review
- The role of E3 ubiquitin ligase HECTD3 in cancer and beyond.Cellular and molecular life sciences : CMLS · 2020Review
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- Small molecule NSC1892 targets the CUL4A/4B-DDB1 interactions and causes impairment of CRL4International journal of biological sciences · 2020Article
- Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk.Frontiers in immunology · 2020Article
- A patent review of the ubiquitin ligase system: 2015-2018.Expert opinion on therapeutic patents · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Decreased levels of cell cycle inhibitor p27(Kip1) due to excessive degradation occur in a variety of aggressive human tumors. Since reduced p27(Kip1) expression has been associated with a poor prognosis in many human cancers and resistance to certain antitumor therapies, elevation of p27(Kip1) expression could improve prognosis and prevent excessive cell proliferation. SCF(Skp2) is one of the major ubiquitin E3 ligases responsible for degradation of p27(Kip1). Ubiquitination of p27(Kip1) also requires a small adaptor protein, Cks1, which facilitates substrate recruitment by bridging the interaction between Skp2 and p27(Kip1). It has been shown previously that a direct interaction between Cks1 and Skp2 is required for p27(Kip1) degradation. Accordingly, perturbation of the Skp2-Cks1 interaction may represent an attractive target for pharmacological intervention. Here we describe a high-throughput AlphaScreen assay for discovering small-molecule inhibitors of the Skp2-Cks1 protein-protein interaction in vitro. Two compounds (NSC689857 and NSC681152) were identified and validated through a structure-activity relationship analysis. Both compounds were also shown to inhibit p27(Kip1) ubiquitination in vitro. These studies demonstrate that disruption of the Skp2-Cks1 interaction provides a viable strategy to prevent p27(Kip1) ubiquitination and may potentially be useful for the control of excessive degradation of this cell cycle inhibitor in tumor cells.
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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.