E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation

Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of...

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Autores principales:	Carcagno, Abel Luis, Giono, Luciana Eugenia, Marazita, Mariela C., Pregi, Nicolás, Cánepa, Eduardo Tomás
Publicado:	2012
Materias:	DNA damage response E2F1 p19INK4d Transcriptional regulation UV irradiation beta tubulin caspase 3 cyclin dependent kinase inhibitor cyclin E protein p191nk4d tamoxifen transcription factor E2F2 unclassified drug animal cell apoptosis article cell cycle arrest cell cycle phase cell proliferation clonogenic assay controlled study DNA binding DNA damage DNA repair DNA responsive element enzyme activity enzyme induction enzyme inhibition gene sequence genetic transfection genomic instability genotoxicity human human cell mitosis nonhuman regulatory mechanism RNA extraction transcription regulation ultraviolet irradiation upregulation Animals Cell Cycle Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA DNA Damage DNA Repair E2F1 Transcription Factor HEK293 Cells Humans Response Elements Transcription, Genetic Transcriptional Activation Ultraviolet Rays
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v366_n1-2_p123_Carcagno http://hdl.handle.net/20.500.12110/paper_03008177_v366_n1-2_p123_Carcagno
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_03008177_v366_n1-2_p123_Carcagno
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spelling	paper:paper_03008177_v366_n1-2_p123_Carcagno2023-06-08T15:27:26Z E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation Carcagno, Abel Luis Giono, Luciana Eugenia Marazita, Mariela C. Pregi, Nicolás Cánepa, Eduardo Tomás DNA damage response E2F1 p19INK4d Transcriptional regulation UV irradiation beta tubulin caspase 3 cyclin dependent kinase inhibitor cyclin E protein p191nk4d tamoxifen transcription factor E2F2 unclassified drug animal cell apoptosis article cell cycle arrest cell cycle phase cell proliferation clonogenic assay controlled study DNA binding DNA damage DNA repair DNA responsive element enzyme activity enzyme induction enzyme inhibition gene sequence genetic transfection genomic instability genotoxicity human human cell mitosis nonhuman regulatory mechanism RNA extraction transcription regulation ultraviolet irradiation upregulation Animals Cell Cycle Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA DNA Damage DNA Repair E2F1 Transcription Factor HEK293 Cells Humans Response Elements Transcription, Genetic Transcriptional Activation Ultraviolet Rays Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK inhibitors, plays a dual role in the DNA damage response, inhibiting cell proliferation and promoting DNA repair. Consistently, p19INK4d has been reported to become upregulated in response to UV irradiation and a great variety of genotoxic agents. Here, this induction is shown to result from a transcriptional stimulatory mechanism that can occur at every phase of the cell cycle except during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this regulation using triplex-forming oligonucleotides that target the E2F response elements present in the p19INK4d promoter also block p19INK4d upregulation and sensitize cells to DNA damage. These results constitute the first description of a mechanism for the induction of p19INK4d in response to UV irradiation and demonstrate the physiological relevance of this regulation following DNA damage. © 2012 Springer Science+Business Media, LLC. Fil:Carcagno, A.L. 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:Marazita, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pregi, N. 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. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v366_n1-2_p123_Carcagno http://hdl.handle.net/20.500.12110/paper_03008177_v366_n1-2_p123_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	DNA damage response E2F1 p19INK4d Transcriptional regulation UV irradiation beta tubulin caspase 3 cyclin dependent kinase inhibitor cyclin E protein p191nk4d tamoxifen transcription factor E2F2 unclassified drug animal cell apoptosis article cell cycle arrest cell cycle phase cell proliferation clonogenic assay controlled study DNA binding DNA damage DNA repair DNA responsive element enzyme activity enzyme induction enzyme inhibition gene sequence genetic transfection genomic instability genotoxicity human human cell mitosis nonhuman regulatory mechanism RNA extraction transcription regulation ultraviolet irradiation upregulation Animals Cell Cycle Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA DNA Damage DNA Repair E2F1 Transcription Factor HEK293 Cells Humans Response Elements Transcription, Genetic Transcriptional Activation Ultraviolet Rays
spellingShingle	DNA damage response E2F1 p19INK4d Transcriptional regulation UV irradiation beta tubulin caspase 3 cyclin dependent kinase inhibitor cyclin E protein p191nk4d tamoxifen transcription factor E2F2 unclassified drug animal cell apoptosis article cell cycle arrest cell cycle phase cell proliferation clonogenic assay controlled study DNA binding DNA damage DNA repair DNA responsive element enzyme activity enzyme induction enzyme inhibition gene sequence genetic transfection genomic instability genotoxicity human human cell mitosis nonhuman regulatory mechanism RNA extraction transcription regulation ultraviolet irradiation upregulation Animals Cell Cycle Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA DNA Damage DNA Repair E2F1 Transcription Factor HEK293 Cells Humans Response Elements Transcription, Genetic Transcriptional Activation Ultraviolet Rays Carcagno, Abel Luis Giono, Luciana Eugenia Marazita, Mariela C. Pregi, Nicolás Cánepa, Eduardo Tomás E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
topic_facet	DNA damage response E2F1 p19INK4d Transcriptional regulation UV irradiation beta tubulin caspase 3 cyclin dependent kinase inhibitor cyclin E protein p191nk4d tamoxifen transcription factor E2F2 unclassified drug animal cell apoptosis article cell cycle arrest cell cycle phase cell proliferation clonogenic assay controlled study DNA binding DNA damage DNA repair DNA responsive element enzyme activity enzyme induction enzyme inhibition gene sequence genetic transfection genomic instability genotoxicity human human cell mitosis nonhuman regulatory mechanism RNA extraction transcription regulation ultraviolet irradiation upregulation Animals Cell Cycle Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA DNA Damage DNA Repair E2F1 Transcription Factor HEK293 Cells Humans Response Elements Transcription, Genetic Transcriptional Activation Ultraviolet Rays
description	Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK inhibitors, plays a dual role in the DNA damage response, inhibiting cell proliferation and promoting DNA repair. Consistently, p19INK4d has been reported to become upregulated in response to UV irradiation and a great variety of genotoxic agents. Here, this induction is shown to result from a transcriptional stimulatory mechanism that can occur at every phase of the cell cycle except during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this regulation using triplex-forming oligonucleotides that target the E2F response elements present in the p19INK4d promoter also block p19INK4d upregulation and sensitize cells to DNA damage. These results constitute the first description of a mechanism for the induction of p19INK4d in response to UV irradiation and demonstrate the physiological relevance of this regulation following DNA damage. © 2012 Springer Science+Business Media, LLC.
author	Carcagno, Abel Luis Giono, Luciana Eugenia Marazita, Mariela C. Pregi, Nicolás Cánepa, Eduardo Tomás
author_facet	Carcagno, Abel Luis Giono, Luciana Eugenia Marazita, Mariela C. Pregi, Nicolás Cánepa, Eduardo Tomás
author_sort	Carcagno, Abel Luis
title	E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
title_short	E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
title_full	E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
title_fullStr	E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
title_full_unstemmed	E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
title_sort	e2f1 induces p19ink4d, a protein involved in the dna damage response, following uv irradiation
publishDate	2012
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v366_n1-2_p123_Carcagno http://hdl.handle.net/20.500.12110/paper_03008177_v366_n1-2_p123_Carcagno
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_version_	1768542036464500736

E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation

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