Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light

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Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations that are highly dependent on its ability to affect gene expression. Among them, the rapid activation of genes coding for two subfamilies of proto-oncoproteins, Fos and Jun, which constitute the AP-1 trans...

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Autores principales:	Tanos, T., Marinissen, M.J., Leskow, F.C., Hochbaum, D., Martinetto, H., Gutkind, J.S., Coso, O.A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2005
Materias:	Activation analysis DNA Genetic engineering Proteins Tissue Ultraviolet radiation Fos activation kinase Gene expression Phosphorylations Rapid activation Biochemical engineering mitogen activated protein kinase p38 oncoprotein proteinase transcription factor AP 1 enzyme inhibitor glutathione transferase hybrid protein isoprotein luciferase protein c fos apoptosis article cell proliferation complex formation DNA repair enzyme phosphorylation enzyme substrate extracellular matrix gene expression regulation genetic transcription human human cell multigene family oncogene c fos priority journal protein domain protein family radiation exposure transactivation transcription regulation ultraviolet radiation active transport animal binding site biological model cell cycle cell fractionation cell line cell nucleus cell strain 3T3 chemistry DNA damage fluorescence microscopy fluorescent antibody technique genetic transfection HeLa cell metabolism mouse phosphorylation polyacrylamide gel electrophoresis reporter gene time two hybrid system Western blotting Active Transport, Cell Nucleus Animals Apoptosis Binding Sites Blotting, Western Cell Cycle Cell Line Cell Nucleus DNA Damage Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors Extracellular Matrix Fluorescent Antibody Technique, Indirect Genes, Reporter Glutathione Transferase Hela Cells Humans Luciferases Mice Microscopy, Fluorescence Models, Biological NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Isoforms Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins Subcellular Fractions Time Factors Trans-Activation (Genetics) Transcription Factor AP-1 Transcription, Genetic Transfection Two-Hybrid System Techniques Ultraviolet Rays
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219258_v280_n19_p18842_Tanos
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00219258_v280_n19_p18842_Tanos
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	Activation analysis DNA Genetic engineering Proteins Tissue Ultraviolet radiation Fos activation kinase Gene expression Phosphorylations Rapid activation Biochemical engineering mitogen activated protein kinase p38 oncoprotein proteinase transcription factor AP 1 DNA enzyme inhibitor glutathione transferase hybrid protein isoprotein luciferase protein c fos transcription factor AP 1 apoptosis article cell proliferation complex formation DNA repair enzyme phosphorylation enzyme substrate extracellular matrix gene expression regulation genetic transcription human human cell multigene family oncogene c fos priority journal protein domain protein family radiation exposure transactivation transcription regulation ultraviolet radiation active transport animal binding site biological model cell cycle cell fractionation cell line cell nucleus cell strain 3T3 chemistry DNA damage fluorescence microscopy fluorescent antibody technique genetic transfection HeLa cell metabolism mouse phosphorylation polyacrylamide gel electrophoresis reporter gene time two hybrid system Western blotting Active Transport, Cell Nucleus Animals Apoptosis Binding Sites Blotting, Western Cell Cycle Cell Line Cell Nucleus DNA DNA Damage Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors Extracellular Matrix Fluorescent Antibody Technique, Indirect Genes, Reporter Glutathione Transferase Hela Cells Humans Luciferases Mice Microscopy, Fluorescence Models, Biological NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Isoforms Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins Subcellular Fractions Time Factors Trans-Activation (Genetics) Transcription Factor AP-1 Transcription, Genetic Transfection Two-Hybrid System Techniques Ultraviolet Rays
spellingShingle	Activation analysis DNA Genetic engineering Proteins Tissue Ultraviolet radiation Fos activation kinase Gene expression Phosphorylations Rapid activation Biochemical engineering mitogen activated protein kinase p38 oncoprotein proteinase transcription factor AP 1 DNA enzyme inhibitor glutathione transferase hybrid protein isoprotein luciferase protein c fos transcription factor AP 1 apoptosis article cell proliferation complex formation DNA repair enzyme phosphorylation enzyme substrate extracellular matrix gene expression regulation genetic transcription human human cell multigene family oncogene c fos priority journal protein domain protein family radiation exposure transactivation transcription regulation ultraviolet radiation active transport animal binding site biological model cell cycle cell fractionation cell line cell nucleus cell strain 3T3 chemistry DNA damage fluorescence microscopy fluorescent antibody technique genetic transfection HeLa cell metabolism mouse phosphorylation polyacrylamide gel electrophoresis reporter gene time two hybrid system Western blotting Active Transport, Cell Nucleus Animals Apoptosis Binding Sites Blotting, Western Cell Cycle Cell Line Cell Nucleus DNA DNA Damage Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors Extracellular Matrix Fluorescent Antibody Technique, Indirect Genes, Reporter Glutathione Transferase Hela Cells Humans Luciferases Mice Microscopy, Fluorescence Models, Biological NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Isoforms Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins Subcellular Fractions Time Factors Trans-Activation (Genetics) Transcription Factor AP-1 Transcription, Genetic Transfection Two-Hybrid System Techniques Ultraviolet Rays Tanos, T. Marinissen, M.J. Leskow, F.C. Hochbaum, D. Martinetto, H. Gutkind, J.S. Coso, O.A. Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
topic_facet	Activation analysis DNA Genetic engineering Proteins Tissue Ultraviolet radiation Fos activation kinase Gene expression Phosphorylations Rapid activation Biochemical engineering mitogen activated protein kinase p38 oncoprotein proteinase transcription factor AP 1 DNA enzyme inhibitor glutathione transferase hybrid protein isoprotein luciferase protein c fos transcription factor AP 1 apoptosis article cell proliferation complex formation DNA repair enzyme phosphorylation enzyme substrate extracellular matrix gene expression regulation genetic transcription human human cell multigene family oncogene c fos priority journal protein domain protein family radiation exposure transactivation transcription regulation ultraviolet radiation active transport animal binding site biological model cell cycle cell fractionation cell line cell nucleus cell strain 3T3 chemistry DNA damage fluorescence microscopy fluorescent antibody technique genetic transfection HeLa cell metabolism mouse phosphorylation polyacrylamide gel electrophoresis reporter gene time two hybrid system Western blotting Active Transport, Cell Nucleus Animals Apoptosis Binding Sites Blotting, Western Cell Cycle Cell Line Cell Nucleus DNA DNA Damage Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors Extracellular Matrix Fluorescent Antibody Technique, Indirect Genes, Reporter Glutathione Transferase Hela Cells Humans Luciferases Mice Microscopy, Fluorescence Models, Biological NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Isoforms Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins Subcellular Fractions Time Factors Trans-Activation (Genetics) Transcription Factor AP-1 Transcription, Genetic Transfection Two-Hybrid System Techniques Ultraviolet Rays
description	Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations that are highly dependent on its ability to affect gene expression. Among them, the rapid activation of genes coding for two subfamilies of proto-oncoproteins, Fos and Jun, which constitute the AP-1 transcription factor, plays a key role in the subsequent regulation of expression of genes involved in DNA repair, cell proliferation, cell cycle arrest, death by apoptosis, and tissue and extracellular matrix remodeling proteases. Besides being regulated at the transcriptional level, Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fos-activating kinases has remained elusive. Here we identify p38 MAPKs as proteins that can associate with c-Fos and phosphorylate its transactivation domain both in vitro and in vivo. This phosphorylation is transduced into changes in its transcriptional ability as p38-activated c-Fos enhances AP1-driven gene expression. Our findings indicate that as a consequence of the activation of stress pathways induced by UV light, endogenous c-Fos becomes a substrate of p38 MAPKs and, for the first time, provide evidence that support a critical role for p38 MAPKs in mediating stress-induced c-Fos phosphorylation and gene transcription activation. Using a specific pharmacological inhibitor for p38α and -β, we found that most likely these two isoforms mediate UV-induced c-Fos phosphorylation in vivo. Thus, these newly described pathways act concomitantly with the activation of c-Jun by JNK/MAPKs, thereby contributing to the complexity of AP1-driven gene transcription regulation.
format	Artículo Artículo publishedVersion
author	Tanos, T. Marinissen, M.J. Leskow, F.C. Hochbaum, D. Martinetto, H. Gutkind, J.S. Coso, O.A.
author_facet	Tanos, T. Marinissen, M.J. Leskow, F.C. Hochbaum, D. Martinetto, H. Gutkind, J.S. Coso, O.A.
author_sort	Tanos, T.
title	Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
title_short	Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
title_full	Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
title_fullStr	Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
title_full_unstemmed	Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light
title_sort	phosphorylation of c-fos by members of the p38 mapk family: role in the ap-1 response to uv light
publishDate	2005
url	http://hdl.handle.net/20.500.12110/paper_00219258_v280_n19_p18842_Tanos
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spelling	paperaa:paper_00219258_v280_n19_p18842_Tanos2023-06-12T16:42:53Z Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light J. Biol. Chem. 2005;280(19):18842-18852 Tanos, T. Marinissen, M.J. Leskow, F.C. Hochbaum, D. Martinetto, H. Gutkind, J.S. Coso, O.A. Activation analysis DNA Genetic engineering Proteins Tissue Ultraviolet radiation Fos activation kinase Gene expression Phosphorylations Rapid activation Biochemical engineering mitogen activated protein kinase p38 oncoprotein proteinase transcription factor AP 1 DNA enzyme inhibitor glutathione transferase hybrid protein isoprotein luciferase protein c fos transcription factor AP 1 apoptosis article cell proliferation complex formation DNA repair enzyme phosphorylation enzyme substrate extracellular matrix gene expression regulation genetic transcription human human cell multigene family oncogene c fos priority journal protein domain protein family radiation exposure transactivation transcription regulation ultraviolet radiation active transport animal binding site biological model cell cycle cell fractionation cell line cell nucleus cell strain 3T3 chemistry DNA damage fluorescence microscopy fluorescent antibody technique genetic transfection HeLa cell metabolism mouse phosphorylation polyacrylamide gel electrophoresis reporter gene time two hybrid system Western blotting Active Transport, Cell Nucleus Animals Apoptosis Binding Sites Blotting, Western Cell Cycle Cell Line Cell Nucleus DNA DNA Damage Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors Extracellular Matrix Fluorescent Antibody Technique, Indirect Genes, Reporter Glutathione Transferase Hela Cells Humans Luciferases Mice Microscopy, Fluorescence Models, Biological NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Isoforms Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins Subcellular Fractions Time Factors Trans-Activation (Genetics) Transcription Factor AP-1 Transcription, Genetic Transfection Two-Hybrid System Techniques Ultraviolet Rays Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations that are highly dependent on its ability to affect gene expression. Among them, the rapid activation of genes coding for two subfamilies of proto-oncoproteins, Fos and Jun, which constitute the AP-1 transcription factor, plays a key role in the subsequent regulation of expression of genes involved in DNA repair, cell proliferation, cell cycle arrest, death by apoptosis, and tissue and extracellular matrix remodeling proteases. Besides being regulated at the transcriptional level, Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fos-activating kinases has remained elusive. Here we identify p38 MAPKs as proteins that can associate with c-Fos and phosphorylate its transactivation domain both in vitro and in vivo. This phosphorylation is transduced into changes in its transcriptional ability as p38-activated c-Fos enhances AP1-driven gene expression. Our findings indicate that as a consequence of the activation of stress pathways induced by UV light, endogenous c-Fos becomes a substrate of p38 MAPKs and, for the first time, provide evidence that support a critical role for p38 MAPKs in mediating stress-induced c-Fos phosphorylation and gene transcription activation. Using a specific pharmacological inhibitor for p38α and -β, we found that most likely these two isoforms mediate UV-induced c-Fos phosphorylation in vivo. Thus, these newly described pathways act concomitantly with the activation of c-Jun by JNK/MAPKs, thereby contributing to the complexity of AP1-driven gene transcription regulation. Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Hochbaum, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martinetto, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2005 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_00219258_v280_n19_p18842_Tanos

Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light

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