E2F1 transcription is induced by genotoxic stress through ATM/ATR activation
E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven t...
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todo:paper_15216543_v61_n5_p537_Carcagno2023-10-03T16:20:37Z E2F1 transcription is induced by genotoxic stress through ATM/ATR activation Carcagno, A.L. Ogara, M.F. Sonzogni, S.V. Marazita, M.C. Sirkin, P.F. Ceruti, J.M. Cánepa, E.T. ATM ATR Cyclin E DNA damage response E2F1 Genotoxic stress Phosphorylation Protein stability Transcriptional regulation UV irradiation ATM protein ATR protein cyclin E transcription factor E2F1 ATR protein, human cell cycle protein cyclin E oligodeoxyribonucleotide protein serine threonine kinase transcription factor E2F1 article controlled study DNA damage gene targeting genetic transcription genotoxicity human human cell protein expression protein phosphorylation protein stability protein synthesis stress cell line DNA damage genetics metabolism Northern blotting phosphorylation radiation exposure transcription initiation ultraviolet radiation Western blotting Blotting, Northern Blotting, Western Cell Cycle Proteins Cell Line Cyclin E DNA Damage E2F1 Transcription Factor Humans Oligodeoxyribonucleotides Phosphorylation Protein-Serine-Threonine Kinases Transcriptional Activation Ultraviolet Rays E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress. © 2009 IUBMB. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15216543_v61_n5_p537_Carcagno |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
ATM ATR Cyclin E DNA damage response E2F1 Genotoxic stress Phosphorylation Protein stability Transcriptional regulation UV irradiation ATM protein ATR protein cyclin E transcription factor E2F1 ATR protein, human cell cycle protein cyclin E oligodeoxyribonucleotide protein serine threonine kinase transcription factor E2F1 article controlled study DNA damage gene targeting genetic transcription genotoxicity human human cell protein expression protein phosphorylation protein stability protein synthesis stress cell line DNA damage genetics metabolism Northern blotting phosphorylation radiation exposure transcription initiation ultraviolet radiation Western blotting Blotting, Northern Blotting, Western Cell Cycle Proteins Cell Line Cyclin E DNA Damage E2F1 Transcription Factor Humans Oligodeoxyribonucleotides Phosphorylation Protein-Serine-Threonine Kinases Transcriptional Activation Ultraviolet Rays |
spellingShingle |
ATM ATR Cyclin E DNA damage response E2F1 Genotoxic stress Phosphorylation Protein stability Transcriptional regulation UV irradiation ATM protein ATR protein cyclin E transcription factor E2F1 ATR protein, human cell cycle protein cyclin E oligodeoxyribonucleotide protein serine threonine kinase transcription factor E2F1 article controlled study DNA damage gene targeting genetic transcription genotoxicity human human cell protein expression protein phosphorylation protein stability protein synthesis stress cell line DNA damage genetics metabolism Northern blotting phosphorylation radiation exposure transcription initiation ultraviolet radiation Western blotting Blotting, Northern Blotting, Western Cell Cycle Proteins Cell Line Cyclin E DNA Damage E2F1 Transcription Factor Humans Oligodeoxyribonucleotides Phosphorylation Protein-Serine-Threonine Kinases Transcriptional Activation Ultraviolet Rays Carcagno, A.L. Ogara, M.F. Sonzogni, S.V. Marazita, M.C. Sirkin, P.F. Ceruti, J.M. Cánepa, E.T. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
topic_facet |
ATM ATR Cyclin E DNA damage response E2F1 Genotoxic stress Phosphorylation Protein stability Transcriptional regulation UV irradiation ATM protein ATR protein cyclin E transcription factor E2F1 ATR protein, human cell cycle protein cyclin E oligodeoxyribonucleotide protein serine threonine kinase transcription factor E2F1 article controlled study DNA damage gene targeting genetic transcription genotoxicity human human cell protein expression protein phosphorylation protein stability protein synthesis stress cell line DNA damage genetics metabolism Northern blotting phosphorylation radiation exposure transcription initiation ultraviolet radiation Western blotting Blotting, Northern Blotting, Western Cell Cycle Proteins Cell Line Cyclin E DNA Damage E2F1 Transcription Factor Humans Oligodeoxyribonucleotides Phosphorylation Protein-Serine-Threonine Kinases Transcriptional Activation Ultraviolet Rays |
description |
E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress. © 2009 IUBMB. |
format |
JOUR |
author |
Carcagno, A.L. Ogara, M.F. Sonzogni, S.V. Marazita, M.C. Sirkin, P.F. Ceruti, J.M. Cánepa, E.T. |
author_facet |
Carcagno, A.L. Ogara, M.F. Sonzogni, S.V. Marazita, M.C. Sirkin, P.F. Ceruti, J.M. Cánepa, E.T. |
author_sort |
Carcagno, A.L. |
title |
E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
title_short |
E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
title_full |
E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
title_fullStr |
E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
title_full_unstemmed |
E2F1 transcription is induced by genotoxic stress through ATM/ATR activation |
title_sort |
e2f1 transcription is induced by genotoxic stress through atm/atr activation |
url |
http://hdl.handle.net/20.500.12110/paper_15216543_v61_n5_p537_Carcagno |
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