Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10801768 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2016 | 42 Pages |
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 Î203-254 leads to confinement of MAGE-D2 to the cytoplasm, while Î248-254 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.
Keywords
CPTNPMNLSDRBUBFDFCFBLNoLSeGFPMAGEMHDCTAPIKKCancer/testis antigenMelanoma antigenCellular stressdense fibrillar componentGranular componentnuclear localization signalNucleolar localization signalUpstream binding factorFibrillarinfibrillar centernucleophosminNucleolusenhanced green fluorescent proteinCell cyclecamptothecinMAP kinases
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Authors
Céline Pirlot, Marc Thiry, Charlotte Trussart, Emmanuel Di Valentin, Jacques Piette, Yvette Habraken,