The MAGE proteins: emerging roles in cell cycle progression, apoptosis, and neurogenetic disease.
Since the identification of the first MAGE gene in 1991, the MAGE family has expanded dramatically, and over 25 MAGE genes have now been identified in humans. The focus of studies on the MAGE proteins has been their potential for cancer immunotherapy, as a result of the finding that peptides derived from MAGE gene products are bound by major histocompatibility complexes and presented on the cell surface of cancer cells. However, the normal physiological role of MAGE proteins has remained a mystery. Recent studies are now beginning to provide insights into MAGE gene function. Necdin acts as a cell cycle regulatory protein and plays a key role in the pathogenesis of Prader-Willi syndrome, a neurogenetic disorder. MAGE-D1, identified as a binding partner for the p75 neurotrophin receptor, the apoptosis inhibitory protein XIAP, and Dlx/MSX homeodomain proteins, blocks cell cycle progression and enhances apoptosis. This review provides an overview of the human MAGE genes and proteins, summarizes recent findings on their cellular roles, and provides a baseline for future studies on this intriguing gene family.
Barker
Philip A
PA
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. philip.barker@mcgill.ca
Salehi
Amir
A
D000818:Animals; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000503:physiopathology*; D017386:Sequence Homology, Amino Acid
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C120897:MAGED1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin