ArticlePloS one2015
MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Prognostic Value of Melanoma-Associated Antigen-A (MAGE-A) Gene Expression in Various Human Cancers: A Systematic Review and Meta-analysis of 7428 Patients and 44 Studies.Molecular diagnosis & therapy · 2020Pooled it
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- Melanoma Antigen Family A (MAGE A) as Promising Biomarkers and Therapeutic Targets in Bladder Cancer.Cancers · 2024Review
- Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma.Frontiers in oncology · 2023Review
- MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-S.Cells · 2022Article
- Overexpression of melanoma-associated antigen A2 has a clinical significance in embryonal carcinoma and is associated with tumor progression.Journal of cancer research and clinical oncology · 2022Article
- Article
- The Dual Roles of MAGE-C2 in p53 Ubiquitination and Cell Proliferation Through E3 Ligases MDM2 and TRIM28.Frontiers in cell and developmental biology · 2022Article
- Targeting cancer testis antigens in synovial sarcoma.Journal for immunotherapy of cancer · 2021Review
- A Preliminary Study of the Cross-Reactivity of Canine MAGE-A with Hominid Monoclonal Antibody 6C1 in Canine Mammary Gland Tumors: An Attractive Target for Cancer Diagnostic, Prognostic and Immunotherapeutic Development in Dogs.Veterinary sciences · 2020Article
- MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells.Journal of hematology & oncology · 2019Article
- Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells.Oncotarget · 2019Article
- Epigenetic regulation of MAGE family in human cancer progression-DNA methylation, histone modification, and non-coding RNAs.Clinical epigenetics · 2018Review
- Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma.Oncology letters · 2018Article
- Expression of MAGE-A and NY-ESO-1 cancer/testis antigens is enriched in triple-negative invasive breast cancers.Histopathology · 2018Article
- Cancer testis antigens as immunogenic and oncogenic targets in breast cancer.Immunotherapy · 2018Review
- MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.Clinical oral investigations · 2018Article
- MAGEA1 interacts with FBXW7 and regulates ubiquitin ligase-mediated turnover of NICD1 in breast and ovarian cancer cells.Oncogene · 2017Article
- MDMX is a prognostic factor for non-small cell lung cancer and regulates its sensitivity to cisplatin.Cellular oncology (Dordrecht, Netherlands) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically.
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