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ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells

ΔNp63α is a potent oncogene in squamous cell carcinomas (SCCs) and a pro-proliferative factor expressed by basal epithelial cells. ΔNp63α functions both as a transcriptional repressor and activator, but it is not clear how these activities contribute to its oncogenic potential. ΔNp63α was proposed t...

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Autores principales: Gallant-Behm, Corrie L., Espinosa, Joaquín M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587441/
https://www.ncbi.nlm.nih.gov/pubmed/23324337
http://dx.doi.org/10.4161/cc.23593
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author Gallant-Behm, Corrie L.
Espinosa, Joaquín M.
author_facet Gallant-Behm, Corrie L.
Espinosa, Joaquín M.
author_sort Gallant-Behm, Corrie L.
collection PubMed
description ΔNp63α is a potent oncogene in squamous cell carcinomas (SCCs) and a pro-proliferative factor expressed by basal epithelial cells. ΔNp63α functions both as a transcriptional repressor and activator, but it is not clear how these activities contribute to its oncogenic potential. ΔNp63α was proposed to function as a dominant negative of the related factor p53. Additionally, ΔNp63α was shown to inactivate its family member TAp73 and mediate recruitment of repressive histone deacetylase (HDAC) complexes to chromatin. Recently, we identified a new mechanism of repression involving recruitment of histone H2A/H2A.Z exchange complexes and H2A.Z deposition at ΔNp63α target genes. Here, we aimed to define the possible co-occurrence of the various repressive mechanisms. In lung SCC cells expressing ΔNp63α, p53 and TAp73, we found that ΔNp63α exerts its pro-proliferative and transcriptional repressive effects in a manner independent of p53, TAp73 and histone H3 and H4 deacetylation. Instead, ΔNp63α target genes are differentiated from non-target genes within the p53 network by incorporation and accumulation of acetylated H2A.Z. These results indicate that ΔNp63α utilizes multiple mechanisms of repression in diverse epithelial and SCC cells.
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spelling pubmed-35874412013-03-13 ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells Gallant-Behm, Corrie L. Espinosa, Joaquín M. Cell Cycle Extra Views ΔNp63α is a potent oncogene in squamous cell carcinomas (SCCs) and a pro-proliferative factor expressed by basal epithelial cells. ΔNp63α functions both as a transcriptional repressor and activator, but it is not clear how these activities contribute to its oncogenic potential. ΔNp63α was proposed to function as a dominant negative of the related factor p53. Additionally, ΔNp63α was shown to inactivate its family member TAp73 and mediate recruitment of repressive histone deacetylase (HDAC) complexes to chromatin. Recently, we identified a new mechanism of repression involving recruitment of histone H2A/H2A.Z exchange complexes and H2A.Z deposition at ΔNp63α target genes. Here, we aimed to define the possible co-occurrence of the various repressive mechanisms. In lung SCC cells expressing ΔNp63α, p53 and TAp73, we found that ΔNp63α exerts its pro-proliferative and transcriptional repressive effects in a manner independent of p53, TAp73 and histone H3 and H4 deacetylation. Instead, ΔNp63α target genes are differentiated from non-target genes within the p53 network by incorporation and accumulation of acetylated H2A.Z. These results indicate that ΔNp63α utilizes multiple mechanisms of repression in diverse epithelial and SCC cells. Landes Bioscience 2013-02-01 /pmc/articles/PMC3587441/ /pubmed/23324337 http://dx.doi.org/10.4161/cc.23593 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Extra Views
Gallant-Behm, Corrie L.
Espinosa, Joaquín M.
ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title_full ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title_fullStr ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title_full_unstemmed ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title_short ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
title_sort δnp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells
topic Extra Views
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587441/
https://www.ncbi.nlm.nih.gov/pubmed/23324337
http://dx.doi.org/10.4161/cc.23593
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