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ZNF185 is a p53 target gene following DNA damage

The transcription factor p53 is a key player in the tumour suppressive DNA damage response and a growing number of target genes involved in these pathways has been identified. p53 has been shown to be implicated in controlling cell motility and its mutant form enhances metastasis by loss of cell dir...

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Autores principales: Smirnov, Artem, Cappello, Angela, Lena, Anna Maria, Anemona, Lucia, Mauriello, Alessandro, Di Daniele, Nicola, Annicchiarico-Petruzzelli, Margherita, Melino, Gerry, Candi, Eleonora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286825/
https://www.ncbi.nlm.nih.gov/pubmed/30446632
http://dx.doi.org/10.18632/aging.101639
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author Smirnov, Artem
Cappello, Angela
Lena, Anna Maria
Anemona, Lucia
Mauriello, Alessandro
Di Daniele, Nicola
Annicchiarico-Petruzzelli, Margherita
Melino, Gerry
Candi, Eleonora
author_facet Smirnov, Artem
Cappello, Angela
Lena, Anna Maria
Anemona, Lucia
Mauriello, Alessandro
Di Daniele, Nicola
Annicchiarico-Petruzzelli, Margherita
Melino, Gerry
Candi, Eleonora
author_sort Smirnov, Artem
collection PubMed
description The transcription factor p53 is a key player in the tumour suppressive DNA damage response and a growing number of target genes involved in these pathways has been identified. p53 has been shown to be implicated in controlling cell motility and its mutant form enhances metastasis by loss of cell directionality, but the p53 role in this context has not yet being investigated. Here, we report that ZNF185, an actin cytoskeleton-associated protein from LIM-family of Zn-finger proteins, is induced following DNA-damage. ChIP-seq analysis, chromatin crosslinking immune-precipitation experiments and luciferase assays demonstrate that ZNF185 is a bona fide p53 target gene. Upon genotoxic stress, caused by DNA-damaging drug etoposide and UVB irradiation, ZNF185 expression is up-regulated and in etoposide-treated cells, ZNF185 depletion does not affect cell proliferation and apoptosis, but interferes with actin cytoskeleton remodelling and cell polarization. Bioinformatic analysis of different types of epithelial cancers from both TCGA and GTEx databases showed a significant decrease in ZNF185 mRNA level compared to normal tissues. These findings are confirmed by tissue micro-array IHC staining. Our data highlight the involvement of ZNF185 and cytoskeleton changes in p53-mediated cellular response to genotoxic stress and indicate ZNF185 as potential biomarker for epithelial cancer diagnosis.
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spelling pubmed-62868252018-12-17 ZNF185 is a p53 target gene following DNA damage Smirnov, Artem Cappello, Angela Lena, Anna Maria Anemona, Lucia Mauriello, Alessandro Di Daniele, Nicola Annicchiarico-Petruzzelli, Margherita Melino, Gerry Candi, Eleonora Aging (Albany NY) Research Paper The transcription factor p53 is a key player in the tumour suppressive DNA damage response and a growing number of target genes involved in these pathways has been identified. p53 has been shown to be implicated in controlling cell motility and its mutant form enhances metastasis by loss of cell directionality, but the p53 role in this context has not yet being investigated. Here, we report that ZNF185, an actin cytoskeleton-associated protein from LIM-family of Zn-finger proteins, is induced following DNA-damage. ChIP-seq analysis, chromatin crosslinking immune-precipitation experiments and luciferase assays demonstrate that ZNF185 is a bona fide p53 target gene. Upon genotoxic stress, caused by DNA-damaging drug etoposide and UVB irradiation, ZNF185 expression is up-regulated and in etoposide-treated cells, ZNF185 depletion does not affect cell proliferation and apoptosis, but interferes with actin cytoskeleton remodelling and cell polarization. Bioinformatic analysis of different types of epithelial cancers from both TCGA and GTEx databases showed a significant decrease in ZNF185 mRNA level compared to normal tissues. These findings are confirmed by tissue micro-array IHC staining. Our data highlight the involvement of ZNF185 and cytoskeleton changes in p53-mediated cellular response to genotoxic stress and indicate ZNF185 as potential biomarker for epithelial cancer diagnosis. Impact Journals 2018-11-16 /pmc/articles/PMC6286825/ /pubmed/30446632 http://dx.doi.org/10.18632/aging.101639 Text en Copyright © 2018 Smirnov et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Smirnov, Artem
Cappello, Angela
Lena, Anna Maria
Anemona, Lucia
Mauriello, Alessandro
Di Daniele, Nicola
Annicchiarico-Petruzzelli, Margherita
Melino, Gerry
Candi, Eleonora
ZNF185 is a p53 target gene following DNA damage
title ZNF185 is a p53 target gene following DNA damage
title_full ZNF185 is a p53 target gene following DNA damage
title_fullStr ZNF185 is a p53 target gene following DNA damage
title_full_unstemmed ZNF185 is a p53 target gene following DNA damage
title_short ZNF185 is a p53 target gene following DNA damage
title_sort znf185 is a p53 target gene following dna damage
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286825/
https://www.ncbi.nlm.nih.gov/pubmed/30446632
http://dx.doi.org/10.18632/aging.101639
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