E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation

Mostrar todas las versiones(3)

Background: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carcagno, A.L., Marazita, M.C., Ogara, M.F., Ceruti, J.M., Sonzogni, S.V., Scassa, M.E., Giono, L.E., Cánepa, E.T.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2011
Materias:	cyclin dependent kinase inhibitor 2D cyclin E transcription factor E2F1 CCNE1 protein, human CDKN2D protein, human oncoprotein animal cell article cell cycle progression cell cycle S phase cell proliferation controlled study embryo human human cell nonhuman promoter region protein expression transcription regulation upregulation animal binding site biological model cell cycle cell line feedback system genetic transcription genetics metabolism molecular genetics nucleotide sequence periodicity protein binding Animals Base Sequence Binding Sites Cell Cycle Cell Line Cell Proliferation Conserved Sequence Cyclin E Cyclin-Dependent Kinase Inhibitor p19 E2F1 Transcription Factor Feedback, Physiological Humans Models, Biological Molecular Sequence Data Oncogene Proteins Periodicity Promoter Regions, Genetic Protein Binding Transcription, Genetic Up-Regulation
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_19326203_v6_n7_p_Carcagno
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_19326203_v6_n7_p_Carcagno
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	cyclin dependent kinase inhibitor 2D cyclin E transcription factor E2F1 CCNE1 protein, human CDKN2D protein, human cyclin dependent kinase inhibitor 2D cyclin E oncoprotein transcription factor E2F1 animal cell article cell cycle progression cell cycle S phase cell proliferation controlled study embryo human human cell nonhuman promoter region protein expression transcription regulation upregulation animal binding site biological model cell cycle cell line cell proliferation feedback system genetic transcription genetics metabolism molecular genetics nucleotide sequence periodicity protein binding upregulation Animals Base Sequence Binding Sites Cell Cycle Cell Line Cell Proliferation Conserved Sequence Cyclin E Cyclin-Dependent Kinase Inhibitor p19 E2F1 Transcription Factor Feedback, Physiological Humans Models, Biological Molecular Sequence Data Oncogene Proteins Periodicity Promoter Regions, Genetic Protein Binding Transcription, Genetic Up-Regulation
spellingShingle	cyclin dependent kinase inhibitor 2D cyclin E transcription factor E2F1 CCNE1 protein, human CDKN2D protein, human cyclin dependent kinase inhibitor 2D cyclin E oncoprotein transcription factor E2F1 animal cell article cell cycle progression cell cycle S phase cell proliferation controlled study embryo human human cell nonhuman promoter region protein expression transcription regulation upregulation animal binding site biological model cell cycle cell line cell proliferation feedback system genetic transcription genetics metabolism molecular genetics nucleotide sequence periodicity protein binding upregulation Animals Base Sequence Binding Sites Cell Cycle Cell Line Cell Proliferation Conserved Sequence Cyclin E Cyclin-Dependent Kinase Inhibitor p19 E2F1 Transcription Factor Feedback, Physiological Humans Models, Biological Molecular Sequence Data Oncogene Proteins Periodicity Promoter Regions, Genetic Protein Binding Transcription, Genetic Up-Regulation Carcagno, A.L. Marazita, M.C. Ogara, M.F. Ceruti, J.M. Sonzogni, S.V. Scassa, M.E. Giono, L.E. Cánepa, E.T. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
topic_facet	cyclin dependent kinase inhibitor 2D cyclin E transcription factor E2F1 CCNE1 protein, human CDKN2D protein, human cyclin dependent kinase inhibitor 2D cyclin E oncoprotein transcription factor E2F1 animal cell article cell cycle progression cell cycle S phase cell proliferation controlled study embryo human human cell nonhuman promoter region protein expression transcription regulation upregulation animal binding site biological model cell cycle cell line cell proliferation feedback system genetic transcription genetics metabolism molecular genetics nucleotide sequence periodicity protein binding upregulation Animals Base Sequence Binding Sites Cell Cycle Cell Line Cell Proliferation Conserved Sequence Cyclin E Cyclin-Dependent Kinase Inhibitor p19 E2F1 Transcription Factor Feedback, Physiological Humans Models, Biological Molecular Sequence Data Oncogene Proteins Periodicity Promoter Regions, Genetic Protein Binding Transcription, Genetic Up-Regulation
description	Background: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. Methodology/Principal Findings: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. Conclusions/Significance: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity. © 2011 Carcagno et al.
format	Artículo Artículo publishedVersion
author	Carcagno, A.L. Marazita, M.C. Ogara, M.F. Ceruti, J.M. Sonzogni, S.V. Scassa, M.E. Giono, L.E. Cánepa, E.T.
author_facet	Carcagno, A.L. Marazita, M.C. Ogara, M.F. Ceruti, J.M. Sonzogni, S.V. Scassa, M.E. Giono, L.E. Cánepa, E.T.
author_sort	Carcagno, A.L.
title	E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
title_short	E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
title_full	E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
title_fullStr	E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
title_full_unstemmed	E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation
title_sort	e2f1-mediated upregulation of p19ink4d determines its periodic expression during cell cycle and regulates cellular proliferation
publishDate	2011
url	http://hdl.handle.net/20.500.12110/paper_19326203_v6_n7_p_Carcagno
work_keys_str_mv	AT carcagnoal e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT marazitamc e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT ogaramf e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT cerutijm e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT sonzognisv e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT scassame e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT gionole e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation AT canepaet e2f1mediatedupregulationofp19ink4ddeterminesitsperiodicexpressionduringcellcycleandregulatescellularproliferation
_version_	1769810354070618112
spelling	paperaa:paper_19326203_v6_n7_p_Carcagno2023-06-12T16:51:30Z E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation PLoS ONE 2011;6(7) Carcagno, A.L. Marazita, M.C. Ogara, M.F. Ceruti, J.M. Sonzogni, S.V. Scassa, M.E. Giono, L.E. Cánepa, E.T. cyclin dependent kinase inhibitor 2D cyclin E transcription factor E2F1 CCNE1 protein, human CDKN2D protein, human cyclin dependent kinase inhibitor 2D cyclin E oncoprotein transcription factor E2F1 animal cell article cell cycle progression cell cycle S phase cell proliferation controlled study embryo human human cell nonhuman promoter region protein expression transcription regulation upregulation animal binding site biological model cell cycle cell line cell proliferation feedback system genetic transcription genetics metabolism molecular genetics nucleotide sequence periodicity protein binding upregulation Animals Base Sequence Binding Sites Cell Cycle Cell Line Cell Proliferation Conserved Sequence Cyclin E Cyclin-Dependent Kinase Inhibitor p19 E2F1 Transcription Factor Feedback, Physiological Humans Models, Biological Molecular Sequence Data Oncogene Proteins Periodicity Promoter Regions, Genetic Protein Binding Transcription, Genetic Up-Regulation Background: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. Methodology/Principal Findings: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. Conclusions/Significance: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity. © 2011 Carcagno et al. Fil:Carcagno, A.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marazita, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ogara, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ceruti, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sonzogni, S.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scassa, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Giono, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v6_n7_p_Carcagno

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation

Ejemplares similares