title: Oncogenic MAGEA-TRIM28 ubiquitin ligase downregulates autophagy by ubiquitinating and degrading AMPK in cancer.
abstract: Autophagy is commonly altered in cancer and has a complicated, but important role in regulation of tumor growth. Autophagy is often tumor suppressive in the early stages of cancer development, but contributes to the late stages of tumor growth. Because of this, putative oncogenes that modulate autophagy signaling are especially interesting. Here we discuss our recent work detailing the function of the MAGEA-TRIM28 ubiquitin ligase as an oncogene product that targets PRKAA1/AMPKα1 for ubiquitination and proteasome-mediated degradation. Degradation of AMPK, a master cellular energy sensor and regulator, by MAGEA-TRIM28 results in significantly reduced autophagy and changes in cellular metabolism, including upregulation of MTOR signaling. Overall, expression of MAGEA3 (or MAGEA6) and degradation of AMPK is sufficient to induce transformation of normal cells and promote multiple hallmarks of cancer.
authors.affiliation: a Departments of Physiology, Pharmacology, and Biochemistry; UT Southwestern ; Dallas , TX , USA.
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Pineda
authors.forename: Patrick Ryan
authors.initials: PR
authors.lastname: Potts
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001343:Autophagy; D015536:Down-Regulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D059748:Proteolysis; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000951:Antigens, Neoplasm; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; KAP1; MAGE; TRIM28; autophagy; cancer; melanoma-antigen; spermatogenesis; testis; ubiquitin