ArticleThe Journal of cell biology2018
A Numb-Mdm2 fuzzy complex reveals an isoform-specific involvement of Numb in breast cancer.
Article in The Journal of cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Tumoral switch in NUMB splicing changes essential transcription pathways and induces malignant properties in tumour cells.Genome biology · 2026Article
- Endocytic Control of Cell-Autonomous and Non-Cell-Autonomous Functions of p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RBFOX2-dependent alternative splicing of Numb regulates Notch signaling during muscle stem cell activation.Stem cell reports · 2026Article
- Synergistic amelioration of cholestatic liver fibrosis by combined total astragalus saponins and AAV8.Frontiers in pharmacology · 2026Article
- The CRL7Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.Nature communications · 2024Article
- Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer.Oncogene · 2023Review
- Structural basis for specific RNA recognition by the alternative splicing factor RBM5.Nature communications · 2023Article
- Article
- ETV7 reduces inflammatory responses in breast cancer cells by repressing the TNFR1/NF-κB axis.Cell death & disease · 2023Article
- BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction.Stem cell research & therapy · 2023Article
- Review
- Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.The Journal of cell biology · 2022Article
- NUMB facilitates autophagy initiation through targeting SCFCell death and differentiation · 2022Article
- NUMB as a Therapeutic Target for Melanoma.The Journal of investigative dermatology · 2022Article
- Numb exon 9 inclusion regulates Integrinβ5 surface expression and promotes breast cancer metastasis.Oncogene · 2022Article
- Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.Molecular systems biology · 2022Article
- Prognostic Biomarker NUMB Is Inhibited by Breast Cancer Cell Exosomes to Promote Breast Cancer Progression.Journal of immunology research · 2022Article
- Article
- Different roles of Numb-p72 and Numb-p65 on the trafficking of metabotropic glutamate receptor 5.Molecular biology reports · 2021Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numb functions as an oncosuppressor by inhibiting Notch signaling and stabilizing p53. This latter effect depends on the interaction of Numb with Mdm2, the E3 ligase that ubiquitinates p53 and commits it to degradation. In breast cancer (BC), loss of Numb results in a reduction of p53-mediated responses including sensitivity to genotoxic drugs and maintenance of homeostasis in the stem cell compartment. In this study, we show that the Numb-Mdm2 interaction represents a fuzzy complex mediated by a short Numb sequence encompassing its alternatively spliced exon 3 (Ex3), which is necessary and sufficient to inhibit Mdm2 and prevent p53 degradation. Alterations in the Numb splicing pattern are critical in BC as shown by increased chemoresistance of tumors displaying reduced levels of Ex3-containing isoforms, an effect that could be mechanistically linked to diminished p53 levels. A reduced level of Ex3-less Numb isoforms independently predicts poor outcome in BCs harboring wild-type p53. Thus, we have uncovered an important mechanism of chemoresistance and progression in p53-competent BCs.
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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.