ArticleMolecular cancer research : MCR2012
Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
- A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- Enhanced Delivery of Aurora Kinase A Inhibitor Alisertib via Tumor-Targeting Immunoliposome Nanocomplex for Improved Treatment of Cancers Including Atypical Teratoid/Rhabdoid Tumor.International journal of nanomedicine · 2026Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- eEF1A2 promotes PTEN-GSK3β-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer.Science signaling · 2024Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment.Cancers · 2022Review
- Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models.Journal of biomedical science · 2021Article
- Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.Oncogene · 2021Review
- The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation.Cell death & disease · 2021Article
- A Regulatory Loop of FBXW7-MYC-PLK1 Controls Tumorigenesis of MYC-Driven Medulloblastoma.Cancers · 2021Article
- Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair.Frontiers in cell and developmental biology · 2021Review
- Article
- FBW7 in hematological tumors.Oncology letters · 2020Review
- Aurora-A mediated phosphorylation of LDHB promotes glycolysis and tumor progression by relieving the substrate-inhibition effect.Nature communications · 2019Article
- Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1.Protein & cell · 2019Article
- The role of aurora A and polo-like kinases in high-risk lymphomas.Blood advances · 2019Review
- APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma.Oncogene · 2019Article
- The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways.Cell reports · 2019Article
- FBXO22 Suppresses Metastasis in Human Renal Cell Carcinoma via Inhibiting MMP-9-Mediated Migration and Invasion and VEGF-Mediated Angiogenesis.International journal of biological sciences · 2019Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The Aurora-A kinase gene is frequently amplified and/or overexpressed in a variety of human cancers, leading to major efforts to develop therapeutic agents targeting this pathway. Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3β. Using a series of truncated Aurora-A proteins and site-directed mutagenesis, we identified distinct FBXW7 and GSK3β-binding sites in Aurora-A. Mutation of critical residues in either site substantially disrupts degradation of Aurora-A. Furthermore, we show that loss of Pten results in the stabilization of Aurora-A by attenuating FBXW7-dependent degradation of Aurora-A through the AKT/GSK3β pathway. Moreover, radiation-induced tumor latency is significantly shortened in Fbxw7(+/-)Pten(+/-) mice as compared with either Fbxw7(+/-) or Pten(+/-) mice, indicating that Fbxw7 and Pten appear to cooperate in suppressing tumorigenesis. Our results establish a novel posttranslational regulatory network in which the Pten and Fbxw7 pathways appear to converge on the regulation of Aurora-A level.
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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.