Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress

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 tha...

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Autores principales:	Peche, L.Y., Ladelfa, M.F., Toledo, M.F., Mano, M., Laiseca, J.E., Schneider, C., Monte, M.
Formato:	JOUR
Materias:	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 green fluorescent protein HDAC1 protein, human histone deacetylase MAGEB2 protein, human MDM2 protein, human 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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219258_v290_n49_p29652_Peche
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00219258_v290_n49_p29652_Peche2023-10-03T14:23:24Z Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress Peche, L.Y. Ladelfa, M.F. Toledo, M.F. Mano, M. Laiseca, J.E. Schneider, C. Monte, M. 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 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. Fil:Ladelfa, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v290_n49_p29652_Peche
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Peche, L.Y. Ladelfa, M.F. Toledo, M.F. Mano, M. Laiseca, J.E. Schneider, C. Monte, M. Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
topic_facet	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
description	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.
format	JOUR
author	Peche, L.Y. Ladelfa, M.F. Toledo, M.F. Mano, M. Laiseca, J.E. Schneider, C. Monte, M.
author_facet	Peche, L.Y. Ladelfa, M.F. Toledo, M.F. Mano, M. Laiseca, J.E. Schneider, C. Monte, M.
author_sort	Peche, L.Y.
title	Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
title_short	Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
title_full	Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
title_fullStr	Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
title_full_unstemmed	Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress
title_sort	human mageb2 protein expression enhances e2f transcriptional activity, cell proliferation, and resistance to ribotoxic stress
url	http://hdl.handle.net/20.500.12110/paper_00219258_v290_n49_p29652_Peche
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_version_	1807318945435222016

Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress

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