ArticleOncogene2012
F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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
44 citing papers in PubMed, 70 citations in OpenAlex.
- Targeted inhibition of FBXL2 confers susceptibility of HER2-negative breast cancer to trastuzumab deruxtecan.Nature cancer · 2026Article
- MicroRNAs as the critical regulators of ubiquitin-proteasome system through F-box protein targeting during tumor progression.Cancer cell international · 2025Review
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- ZNF652 exerts a tumor suppressor role in lung cancer by transcriptionally downregulating cyclin D3.Cell death & disease · 2024Article
- Impaired cyclin D3 protein degradation contributes to trastuzumab resistance in HER2 positive breast cancer.Medical oncology (Northwood, London, England) · 2024Article
- Inhibition of USP10 induces myeloma cell apoptosis by promoting cyclin D3 degradation.Acta pharmacologica Sinica · 2023Article
- Review
- The Long-Lost Ligase: CRL4DNA and cell biology · 2021Article
- FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.Nature communications · 2021Article
- Transcriptomic Properties of HER2+ Ductal Carcinoma In Situ of the Breast Associate with Absence of Immune Cells.Biology · 2021Article
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- The FBXL family of F-box proteins: variations on a theme.Open biology · 2020Article
- Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction withMolecular and cellular biology · 2020Article
- The role of ubiquitination in tumorigenesis and targeted drug discovery.Signal transduction and targeted therapy · 2020Review
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- Circular RNA SMARCA5 inhibits gastric cancer progression through targeting the miR-346/ FBXL2 axis.RSC advances · 2019Article
- EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains.Nature genetics · 2019Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Tumor suppressive CaCell stress · 2017Article
- miRNA-346 promotes proliferation, migration and invasion in liver cancer.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulated behavior of cell cycle proteins and their control by ubiquitin E3 ligases is an emerging theme in human lung cancer. Here, we identified and characterized the activity of a novel F-box protein, termed FBXL2, belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family. Ectopically expressed FBXL2 triggered G2/M-phase arrest, induced chromosomal anomalies and increased apoptosis of transformed lung epithelia by mediating polyubiquitination and degradation of the mitotic regulator, cyclin D3. Unlike other F-box proteins that target phosphodegrons within substrates, FBXL2 uniquely recognizes a canonical calmodulin (CaM)-binding motif within cyclin D3 to facilitate its polyubiquitination. CaM bound and protected cyclin D3 from FBXL2 by direct intermolecular competition with the F-box protein for access within this motif. The chemotherapeutic agent vinorelbine increased apoptosis of human lung carcinoma cells by inducing FBXL2 expression and cyclin D3 degradation, an effect accentuated by CaM knockdown. Depletion of endogenous FBXL2 stabilized cyclin D3 levels, accelerated cancer cell growth and increased cell viability after vinorelbine treatment. Last, ectopic expression of FBXL2 significantly inhibited the growth and migration of tumorogenic cells and tumor formation in athymic nude mice. These observations implicate SCF(FBXL2) as an indispensible regulator of mitosis that serves as a tumor suppressor.
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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.