ArticleOncogene2013
Foxo3a transcription factor is a negative regulator of Skp2 and Skp2 SCF complex.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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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.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Epigenetic regulation of NR5A2 influences colorectal cancer cell stemness via a stemness-related transcription factor NANOG.Cell communication and signaling : CCS · 2025Article
- Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.Frontiers in pharmacology · 2023Review
- Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality.Cell death & disease · 2022Article
- Ingestion of hemozoin by peripheral blood mononuclear cells alters temporal gene expression of ubiquitination processes.Biochemistry and biophysics reports · 2022Article
- Review
- Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma.Cancer biology & medicine · 2021Article
- FOXO transcription factor family in cancer and metastasis.Cancer metastasis reviews · 2020Review
- Autophagy and synaptic plasticity: epigenetic regulation.Current opinion in neurobiology · 2019Review
- Article
- Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors.Science signaling · 2018Article
- Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced Cell Cycle Arrest in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2018Article
- Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer.Molecular cancer · 2017Article
- LXR activation causes G1/S arrest through inhibiting SKP2 expression in MIN6 pancreatic beta cells.Endocrine · 2016Article
- Article
- Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence.Cell death and differentiation · 2014Article
- The expression and prognosis of FOXO3a and Skp2 in human ovarian cancer.Medical oncology (Northwood, London, England) · 2012Article
- p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance.Frontiers in oncology · 2012Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Skp2 (S-phase kinase-associated protein-2) SCF complex displays E3 ligase activity and oncogenic activity by regulating protein ubiquitination and degradation, in turn regulating cell cycle entry, senescence and tumorigenesis. The maintenance of the integrity of Skp2 SCF complex is critical for its E3 ligase activity. The Skp2 F-box protein is a rate-limiting step and key factor in this complex, which binds to its protein substrates and triggers ubiquitination and degradation of its substrates. Skp2 is found to be overexpressed in numerous human cancers, which has an important role in tumorigenesis. The molecular mechanism by which the function of Skp2 and Skp2 SCF complex is regulated remains largely unknown. Here we show that Foxo3a transcription factor is a novel and negative regulator of Skp2 SCF complex. Foxo3a is found to be a transcriptional repressor of Skp2 gene expression by directly binding to the Skp2 promoter, thereby inhibiting Skp2 protein expression. Surprisingly, we found for the first time that Foxo3a also displays a transcription-independent activity by directly interacting with Skp2 and disrupting Skp2 SCF complex formation, in turn inhibiting Skp2 SCF E3 ligase activity and promoting p27 stability. Finally, we show that the oncogenic activity of Skp2 is repressed by Foxo3a overexpression. Our results not only reveal novel insights into how Skp2 SCF complex is regulated, but also establish a new role for Foxo3a in tumor suppression through a transcription-dependent and independent manner.
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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.