title: Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress.
abstract: 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. We show that MageB2 counteracts 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.
authors.affiliation: From the Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Leticia Y
authors.initials: LY
authors.lastname: Peche
authors.affiliation: the Departamento de Química Biológica and Instituto de Química Biológica Ciencias Exactas y Naturales/Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Ladelfa
authors.affiliation: the Departamento de Química Biológica and Instituto de Química Biológica Ciencias Exactas y Naturales/Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Toledo
authors.affiliation: the International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34149 Trieste, Italy, and.
authors.forename: Miguel
authors.initials: M
authors.lastname: Mano
authors.affiliation: the Departamento de Química Biológica and Instituto de Química Biológica Ciencias Exactas y Naturales/Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: Julieta E
authors.initials: JE
authors.lastname: Laiseca
authors.affiliation: From the Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, 34149 Trieste, Italy, the Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, p.le Kolbe 4, 33100 Udine, Italy claudio.schneider@lncib.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Schneider
authors.affiliation: the Departamento de Química Biológica and Instituto de Química Biológica Ciencias Exactas y Naturales/Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina, mmonte@qb.fcen.uba.ar.
authors.forename: Martín
authors.initials: M
authors.lastname: Monte
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000378:metabolism; D049109:Cell Proliferation; D003609:Dactinomycin / Q000737:chemistry; D050684:E2F Transcription Factors / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D050684:E2F Transcription Factors; C072012:MAGEB2 protein, human; D009363:Neoplasm Proteins; D049452:Green Fluorescent Proteins; D003609:Dactinomycin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases
keywords: E2F transcription factor; cancer biology; cell proliferation; histone deacetylase 1 (HDAC1); molecular cell biology