ArticlePloS one2019
Cbl interacts with multiple E2s in vitro and in cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Synergistic lethality of combination treatment with Trop2-directed antibody-drug conjugate sacituzumab govitecan and TRAIL agonists in triple negative breast cancer.Breast cancer research : BCR · 2026Article
- Loss of Flotillin-2 enhances trastuzumab emtansine internalization and cytotoxicity by relieving negative regulation of HER2 internalization in HER2-amplified cancers.bioRxiv : the preprint server for biology · 2026Article
- Article
- EGFR amplification and PI3K pathway mutations identify a subset of breast cancers that synergistically respond to EGFR and PI3K inhibition.bioRxiv : the preprint server for biology · 2025Article
- CBL-mediated AQP1 ubiquitination aggravates kidney-yang deficiency syndrome by promoting lipid metabolism dysregulation.European journal of medical research · 2025Article
- The role of ubiquitin-conjugating enzyme in the process of spermatogenesis.Reproductive biology and endocrinology : RB&E · 2024Review
- High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality: A case report.World journal of clinical cases · 2024Article
- A multilevel investigation to reveal the regulatory mechanism of lignin accumulation in juice sac granulation of pomelo.BMC plant biology · 2024Article
- A Modular Turn-On Strategy to Profile E2-Specific Ubiquitination Events in Living Cells.Angewandte Chemie (International ed. in English) · 2024Article
- miR-379-5p affects breast cancer cell behavior by targeting UBE2E3 ubiquitin conjugating enzyme.PloS one · 2024Article
- [CBL inhibits proliferation and invasion of breast cancer cells by ubiquitylation-mediated degradation of NCK2].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases.Frontiers in endocrinology · 2022Review
- The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution.Frontiers in cell and developmental biology · 2022Review
- In Vitro Ubiquitination Platform Identifies Methyl Ellipticiniums as Ubiquitin Ligase Inhibitors.SLAS discovery : advancing life sciences R & D · 2021Article
- Evolution of an Amniote-Specific Mechanism for Modulating Ubiquitin Signaling via Phosphoregulation of the E2 Enzyme UBE2D3.Molecular biology and evolution · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Many receptor tyrosine kinases (RTKs, such as EGFR, MET) are negatively regulated by ubiquitination and degradation mediated by Cbl proteins, a family of RING finger (RF) ubiquitin ligases (E3s). Loss of Cbl protein function is associated with malignant transformation driven by increased RTK activity. RF E3s, such as the Cbl proteins, interact with a ubiquitin-conjugating enzyme (E2) to confer specificity to the ubiquitination process and direct the transfer of ubiquitin from the E2 to one or more lysines on the target proteins. Using in vitro E3 assays and yeast two-hybrid screens, we found that Ube2d, Ube2e families, Ube2n/2v1, and Ube2w catalyze autoubiquitination of the Cbl protein and Ube2d2, Ube2e1, and Ube 2n/2v1 catalyze Cbl-mediated substrate ubiquitination of the EGFR and SYK. Phosphorylation of the Cbl protein by by Src resulted in increased E3 activity compared to unphosphorylated cbl or Cbl containing a phosphomimetic Y371E mutation. Ubiquitin chain formation depended on the E2 tested with Cbl with Ube2d2 forming both K48 and K63 linked chains, Ube2n/2v1 forming only K63 linked chains, and Ube2w inducing monoubiquitination. In cells, the Ube2d family, Ube2e family, and Ube2n/2v1 contributed to EGFR ubiquitination. Our data suggest that multiple E2s can interact with Cbl and modulate its E3 activity in vitro and in cells.
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