ArticleOncogene2011
Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3ɛ.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.Cell death & disease · 2024Review
- Tumor suppressor mediated ubiquitylation of hnRNPK is a barrier to oncogenic translation.Nature communications · 2022Article
- The E3 Ubiquitin Ligase Fbxo4 Functions as a Tumor Suppressor: Its Biological Importance and Therapeutic Perspectives.Cancers · 2022Review
- The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway.Cell death discovery · 2022Article
- Degradation strategy of cyclin D1 in cancer cells and the potential clinical application.Frontiers in oncology · 2022Review
- Unique N-Terminal Interactions Connect F-BOX STRESS INDUCED (FBS) Proteins to a WD40 Repeat-like Protein Pathway in Arabidopsis.Plants (Basel, Switzerland) · 2021Article
- Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy.Cell death & disease · 2021Review
- The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.International journal of molecular sciences · 2021Review
- Gatekeepers of the Gut: The Roles of Proteasomes at the Gastrointestinal Barrier.Biomolecules · 2021Review
- The apple 14-3-3 protein MdGRF11 interacts with the BTB protein MdBT2 to regulate nitrate deficiency-induced anthocyanin accumulation.Horticulture research · 2021Article
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- 14-3-3ζ binds to and stabilizes phospho-beclin 1Journal of cellular and molecular medicine · 2020Article
- 14-3-3ζ binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells.Cancer medicine · 2018Article
- Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential for cell cycle progression through G1 in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome.PLoS pathogens · 2018Article
- Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma.Nature communications · 2017Article
- Cyclin D1, cancer progression, and opportunities in cancer treatment.Journal of molecular medicine (Berlin, Germany) · 2016Review
- Recent advances in SCF ubiquitin ligase complex: Clinical implications.Biochimica et biophysica acta · 2016Review
- Ubiquitin proteasome system research in gastrointestinal cancer.World journal of gastrointestinal oncology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fbx4 is an F-box constituent of Skp-Cullin-F-box (SCF) ubiquitin ligases that directs ubiquitylation of cyclin D1. Ubiquitylation of cyclin D1 requires phosphorylation of both cyclin D1 and Fbx4 by GSK3β. GSK3β-mediated phosphorylation of Fbx4 Ser12 during the G1/S transition regulates Fbx4 dimerization, which in turn governs Fbx4-driven E3 ligase activity. In esophageal carcinomas that overexpress cyclin D1, Fbx4 is subject to inactivating mutations that specifically disrupt dimerization, highlighting the biological significance of this regulatory mechanism. In an effort to elucidate the mechanisms that regulate dimerization, we sought to identify proteins that differentially bind to wild-type Fbx4 versus a cancer-derived dimerization-deficient mutant. We provide evidence that phosphorylation of Ser12 generates a docking site for 14-3-3ɛ. 14-3-3ɛ binds to endogenous Fbx4 and this association is impaired by mutations that target either Ser8 or Ser12 in Fbx4, suggesting that this N-terminal motif in Fbx4 directs its interaction with 14-3-3ɛ. Knockdown of 14-3-3ɛ inhibited Fbx4 dimerization, reduced SCF(Fbx4) E3 ligase activity and stabilized cyclin D1. Collectively, the current results suggest a model wherein 14-3-3ɛ binds to Ser12-phosphorylated Fbx4 to mediate dimerization and function.
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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.