Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress.

Autor:	Peche LY; From the Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, 34149 Trieste, Italy., Ladelfa MF; 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., Toledo MF; 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., Mano M; the International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34149 Trieste, Italy, and., Laiseca JE; 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., Schneider C; 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., Monte M; 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.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Dec 04; Vol. 290 (49), pp. 29652-62. Date of Electronic Publication: 2015 Oct 14.
DOI:	10.1074/jbc.M115.671982
Abstrakt:	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. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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