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MageB2 belongs to the melanoma antigen gene (MAGE-I) family of tumor-specific antigens. Expression of this gene has been detected in human tumors of different origins. However, little is known about the protein function and how its expression affects tumor cell phenotypes. In this work, we found that human MageB2 protein promotes tumor cell proliferation in a p53-independent fashion, as observed both in cultured cells and growing tumors in mice. Gene expression analysis showed that MageB2 enhances the activity of E2F transcription factors. Mechanistically, the activation of E2Fs is related to the ability of MageB2 to interact with the E2F inhibitor HDAC1. Cellular distribution of MageB2 protein includes the nucleoli. Nevertheless, ribotoxic drugs rapidly promote its nucleolar exit.Weshow that MageB2 counter acts E2F inhibition by ribosomal proteins independently of Mdm2 expression. Importantly, MageB2 plays a critical role in impairing cell cycle arrest in response to Actinomycin D. The data presented here support a relevant function for human MageB2 in cancer cells both under cycling and stressed conditions, presenting a distinct functional feature with respect to other characterized MAGE-I proteins. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.


Documento: Artículo
Título:Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
Autor:Peche, L.Y.; Ladelfa, M.F.; Toledo, M.F.; Mano, M.; Laiseca, J.E.; Schneider, C.; Monte, M.
Filiación:Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, Trieste, 34149, Italy
Departamento de Química Biológica, Instituto de Química Biológica Ciencias Exactas y Naturales, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, 1428, Argentina
International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste, 34149, Italy
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, p.le Kolbe 4, Udine, 33100, Italy
Palabras clave:Antigens; Cell proliferation; Cells; Cytology; Genes; Proteins; Transcription; Tumors; Cell-cycle arrest; Cellular distributions; Different origins; Functional features; Gene expression analysis; Protein expressions; Ribosomal proteins; Transcriptional activity; Gene expression; dactinomycin; histone deacetylase 1; melanoma antigen B2; protein MDM2; protein p53; small interfering RNA; transcription factor E2F; transcription factor E2F1; trichostatin A; tumor antigen; unclassified drug; antineoplastic agent; dactinomycin; green fluorescent protein; HDAC1 protein, human; histone deacetylase; MAGEB2 protein, human; MDM2 protein, human; protein MDM2; transcription factor E2F; tumor antigen; tumor protein; animal cell; animal experiment; animal model; animal tissue; Article; cancer cell culture; cell cycle arrest; cell proliferation; cellular stress response; colorectal cancer cell line; controlled study; drug efficacy; drug response; embryo; gene expression; gene silencing; human; human cell; in vitro study; in vivo study; melanoma; melanoma cell line; mouse; nonhuman; nucleolus; priority journal; protein expression; protein localization; protein protein interaction; transcription regulation; tumor growth; animal; C57BL mouse; cell cycle; chemistry; experimental melanoma; fibroblast; gene expression regulation; HCT 116 cell line; HEK293 cell line; metabolism; ribosome; Animals; Antigens, Neoplasm; Antineoplastic Agents; Cell Cycle; Cell Nucleolus; Cell Proliferation; Dactinomycin; E2F Transcription Factors; Fibroblasts; Gene Expression Regulation; Green Fluorescent Proteins; HCT116 Cells; HEK293 Cells; Histone Deacetylase 1; Histone Deacetylases; Humans; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Proto-Oncogene Proteins c-mdm2; Ribosomes
Página de inicio:29652
Página de fin:29662
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
CAS:dactinomycin, 1402-38-6, 1402-58-0, 50-76-0; trichostatin A, 58880-19-6; histone deacetylase, 9076-57-7; Antigens, Neoplasm; Antineoplastic Agents; Dactinomycin; E2F Transcription Factors; Green Fluorescent Proteins; HDAC1 protein, human; Histone Deacetylase 1; Histone Deacetylases; MAGEB2 protein, human; MDM2 protein, human; Neoplasm Proteins; Proto-Oncogene Proteins c-mdm2


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---------- APA ----------
Peche, L.Y., Ladelfa, M.F., Toledo, M.F., Mano, M., Laiseca, J.E., Schneider, C. & Monte, M. (2015) . Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress. Journal of Biological Chemistry, 290(49), 29652-29662.
---------- CHICAGO ----------
Peche, L.Y., Ladelfa, M.F., Toledo, M.F., Mano, M., Laiseca, J.E., Schneider, C., et al. "Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress" . Journal of Biological Chemistry 290, no. 49 (2015) : 29652-29662.
---------- MLA ----------
Peche, L.Y., Ladelfa, M.F., Toledo, M.F., Mano, M., Laiseca, J.E., Schneider, C., et al. "Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress" . Journal of Biological Chemistry, vol. 290, no. 49, 2015, pp. 29652-29662.
---------- VANCOUVER ----------
Peche, L.Y., Ladelfa, M.F., Toledo, M.F., Mano, M., Laiseca, J.E., Schneider, C., et al. Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress. J. Biol. Chem. 2015;290(49):29652-29662.