ArticleNature communications2017
The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 84 citations in OpenAlex.
- Cell-cycle-dependent regulation of DNA end resection by PLK1 and PLK3 without CtIP level modulation.iScience · 2026Article
- miR-452-5p promotes systemic lupus erythematosus-induced inflammatory responses by downregulating RBL2 and impairing Treg development.Immunologic research · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Review
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Targeting Skp2 by Tanshinone IIA overcomes chemoresistance in colorectal cancer.Cell biology and toxicology · 2025Article
- The TRIM22-CDT2 axis is the key mediator of the p53-Rb signals in growth control of HPV-positive cervical carcinoma cells.Neoplasia (New York, N.Y.) · 2025Article
- FOXP2 suppresses gastric cancer progression by transcriptionally repressing FBXW2 via WASL degradation.Cell death discovery · 2025Article
- Identification of E3 Ubiquitin Ligase Substrates Using Biotin Ligase-Based Proximity Labeling Approaches.Biomedicines · 2025Review
- Involvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.Genes & diseases · 2025Review
- FBXW2 inhibits the progression of gastric cancer via promoting β-catenin ubiquitylation.International journal of medical sciences · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- Analysis of Fbox substrate adapter proteins usingComputational and structural biotechnology journal · 2025Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer.Biology direct · 2024Article
- Pivotal Role of FBXW4 in Glioma Progression and Prognosis.Genetics research · 2024Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.Cell death & disease · 2023Article
- FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation.Oncogene · 2023Article
- All-Trans Retinoic Acid Promotes a Tumor Suppressive OTUD6B-β-TrCP-SNAIL Axis in Esophageal Squamous Cell Carcinoma and Enhances Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
β-TrCP and SKP2 are two well-studied F-box proteins, which often act as oncogenes. Whether and how they communicate with each other is unknown. Here we report that FBXW2, a poorly characterized F-box, is a substrate of β-TrCP1 and an E3 ligase for SKP2. While β-TrCP1 promotes FBXW2 ubiquitylation and shortens its half-life, FBXW2 does the same to SKP2. FBXW2 has tumour suppressor activity against lung cancer cells and blocks oncogenic function of both β-TrCP1 and SKP2. The levels of β-TrCP1-FBXW2-SKP2 are inversely correlated during cell cycle with FBXW2 and β-TrCP/SKP2 being high or low, respectively, in arrested cells, whereas the opposite is true in proliferating cells. Consistently, FBXW2 predicts a better patient survival, whereas β-TrCP1 and SKP2 predict a worse survival. Finally, the gain- and loss-of-function mutations of FBXW2 are found in various human cancers. Collectively, our data show that the β-TrCP-FBXW2-SKP2 axis forms an oncogene-tumour suppressor-oncogene cascade to control cancer cell growth with FBXW2 acting as a tumour suppressor by promoting SKP2 degradation.
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