Cellular and disease functions of the Prader–Willi Syndrome gene MAGEL2
Open accessAbstract
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader–Willi Syndrome (PWS) and Schaaf–Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme. The MAGEL2-USP7-TRIM27 (or MUST) complex facilitates the retromer recycling pathway through ubiquitination and activation of the WASH actin nucleation promoting factor. This review provides an overview of the MAGE protein family of ubiquitin ligases regulators and details the molecular and cellular role of MAGEL2 in ubiquitination, actin regulation and endosomal sorting processes, as well as MAGEL2 implications in PWS and SHFYNG disorders. The physiological functions of MAGEL2, elucidated through the study of Magel2 knockout mouse models, are also discussed.
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Not all MAGE E3 ligases are tumour specific.
“Although not all MAGE E3 ligases are tumour specific159”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [159]
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- [13]López-Sánchez N González-Fernández Z Niinobe M Yoshikawa K Frade JM Single mage gene in the chicken genome encodes CMage, a protein with functional similarities to mammalian type II Mage proteins Physiological Genomics 2007 30 2 156 71 17374844
- [83]Zaman MMU Nomura T Takagi T Okamura T Jin W Shinagawa T Ubiquitination-Deubiquitination by the TRIM27-USP7 Complex Regulates Tumor Necrosis Factor Alpha-Induced Apoptosis Molecular and Cellular Biology 2013 33 24 4971 84 24144979 PMC3889550
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Леонидовна, Д. Е., Маркова, Т. В., Bostanova, F., Kuchina, A., Бессонова, Л. А., Melnik, E. A., Забненкова, В. В., Рыжкова, О. П., & Agranovich, O. Е. (2024) · Neuromuscular Diseases · doi:10.17650/2222-8721-2024-14-1-42-50 · Cited by 2 · see citing works
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Development of Next Generation Cell-Permeable Peptide Inhibitors for the Oncological Target MAGE-A4
Lim, J., Chiou, L. F., Novy, B., Chow, E. J., Norris-Drouin, J. L., Hardy, P. B., Popov, K., Vaziri, C., Bowers, A. A., & Pearce, K. H. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01540 · Cited by 1 · see citing works
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The role of genetics and molecular mechanisms in early onset scoliosis
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Evolutionary and Expression Analysis of the Pig MAGE Gene Family
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Genetic Syndromes of Hypothalamic Dysfunction
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- Authors
- Tacer, K. F., & Potts, P. R.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Potts, Patrick Ryan
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2017-06-16
- Volume
- 474
- Issue
- 13
- Pages
- 2177-2190
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC5594744
- OpenAlex
- W2626482316
- Cited by
- 81
- References
- 129
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 14 · 2021: 11 · 2020: 13 · 2019: 8 · 2018: 5
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM111332)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- MAGEL2, Prader-Willi syndrome, Schaaf-Yang syndrome, genomic imprinting, endosomal recycling, TRIM27, USP7, ubiquitination, actin regulation, hypothalamus
- MeSH terms
- Humans, Prader-Willi Syndrome, Proteins, Endosomes, Protein Transport, Intracellular Signaling Peptides and Proteins, Ubiquitination, Intrinsically Disordered Proteins
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