title: Melanoma antigen-D2: A nucleolar protein undergoing delocalization during cell cycle and after cellular stress.
abstract: Melanoma antigen D2 (MAGE-D2) is recognized as a cancer diagnostic marker; however, it has poorly characterized functions. Here, we established its intracellular localization and shuttling during cell cycle progression and in response to cellular stress. In normal conditions, MAGE-D2 is present in the cytoplasm, nucleoplasm, and nucleoli. Within the latter, MAGE-D2 is mostly found in the granular and the dense fibrillar components, and it interacts with nucleolin. Transfection of MAGE-D2 deletion mutants demonstrated that Δ203-254 leads to confinement of MAGE-D2 to the cytoplasm, while Δ248-254 prevents its accumulation in nucleoli but still allows its presence in the nucleoplasm. Consequently, this short sequence belongs to a nucleolar localization signal. MAGE-D2 deletion does not alter the nucleolar organization or rRNA levels. However, its intracellular localization varies with the cell cycle in a different kinetic than nucleolin. After genotoxic and nucleolar stresses, MAGE-D2 is excluded from nucleoli and concentrates in the nucleoplasm. We demonstrated that its camptothecin-related delocalization results from two distinct events: a rapid nucleolar release and a slower phospho-ERK-dependent cytoplasm to nucleoplasm translocation, which results from an increased flux from the cytoplasm to nucleoplasm. In conclusion, MAGE-D2 is a dynamic protein whose shuttling properties could suggest a role in cell cycle regulation.
authors.affiliation: Laboratory of Virology and Immunology, GIGA-Signal Transduction, GIGA-B34, University of Liège, Liège, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Pirlot
authors.affiliation: Unit of Cell and Tissue Biology, GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: Laboratory of Virology and Immunology, GIGA-Signal Transduction, GIGA-B34, University of Liège, Liège, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Trussart
authors.affiliation: GIGA-Viral Vector Platform, University of Liège, Liège, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Di Valentin
authors.affiliation: Laboratory of Virology and Immunology, GIGA-Signal Transduction, GIGA-B34, University of Liège, Liège, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.affiliation: Laboratory of Virology and Immunology, GIGA-Signal Transduction, GIGA-B34, University of Liège, Liège, Belgium. Electronic address: yvette.habraken@ulg.ac.be.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Habraken
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D021381:Protein Transport; D013312:Stress, Physiological / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; C451414:MAGED2 protein, human
keywords: Camptothecin; Cell cycle; Cellular stress; MAP kinases; Melanoma antigen protein; Nucleolus