Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents

The gene <i>TP53</i>, which encodes the tumor suppressor protein p53, is mutated in about 50% of cancers. In response to cell stressors like DNA damage and after treatment with DNA-damaging therapeutic agents, p53 acts as a transcription factor to activate subsets of target genes which c...

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Autores principales:	Lindsey Carlsen, Wafik S. El-Deiry
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	p53 chemotherapy radiation target selectivity DNA damage Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/63e53515f0ec4079b1faa8341d961d21
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spelling	oai:doaj.org-article:63e53515f0ec4079b1faa8341d961d212021-11-11T17:15:50ZDifferential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents10.3390/ijms2221118281422-00671661-6596https://doaj.org/article/63e53515f0ec4079b1faa8341d961d212021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11828https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The gene <i>TP53</i>, which encodes the tumor suppressor protein p53, is mutated in about 50% of cancers. In response to cell stressors like DNA damage and after treatment with DNA-damaging therapeutic agents, p53 acts as a transcription factor to activate subsets of target genes which carry out cell fates such as apoptosis, cell cycle arrest, and DNA repair. Target gene selection by p53 is controlled by a complex regulatory network whose response varies across contexts including treatment type, cell type, and tissue type. The molecular basis of target selection across these contexts is not well understood. Knowledge gained from examining p53 regulatory network profiles across different DNA-damaging agents in different cell types and tissue types may inform logical ways to optimally manipulate the network to encourage p53-mediated tumor suppression and anti-tumor immunity in cancer patients. This may be achieved with combination therapies or with p53-reactivating targeted therapies. Here, we review the basics of the p53 regulatory network in the context of differential responses to DNA-damaging agents; discuss recent efforts to characterize differential p53 responses across treatment types, cell types, and tissue types; and examine the relevance of evaluating these responses in the tumor microenvironment. Finally, we address open questions including the potential relevance of alternative p53 transcriptional functions, p53 transcription-independent functions, and p53-independent functions in the response to DNA-damaging therapeutics.Lindsey CarlsenWafik S. El-DeiryMDPI AGarticlep53chemotherapyradiationtarget selectivityDNA damageBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11828, p 11828 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	p53 chemotherapy radiation target selectivity DNA damage Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	p53 chemotherapy radiation target selectivity DNA damage Biology (General) QH301-705.5 Chemistry QD1-999 Lindsey Carlsen Wafik S. El-Deiry Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
description	The gene <i>TP53</i>, which encodes the tumor suppressor protein p53, is mutated in about 50% of cancers. In response to cell stressors like DNA damage and after treatment with DNA-damaging therapeutic agents, p53 acts as a transcription factor to activate subsets of target genes which carry out cell fates such as apoptosis, cell cycle arrest, and DNA repair. Target gene selection by p53 is controlled by a complex regulatory network whose response varies across contexts including treatment type, cell type, and tissue type. The molecular basis of target selection across these contexts is not well understood. Knowledge gained from examining p53 regulatory network profiles across different DNA-damaging agents in different cell types and tissue types may inform logical ways to optimally manipulate the network to encourage p53-mediated tumor suppression and anti-tumor immunity in cancer patients. This may be achieved with combination therapies or with p53-reactivating targeted therapies. Here, we review the basics of the p53 regulatory network in the context of differential responses to DNA-damaging agents; discuss recent efforts to characterize differential p53 responses across treatment types, cell types, and tissue types; and examine the relevance of evaluating these responses in the tumor microenvironment. Finally, we address open questions including the potential relevance of alternative p53 transcriptional functions, p53 transcription-independent functions, and p53-independent functions in the response to DNA-damaging therapeutics.
format	article
author	Lindsey Carlsen Wafik S. El-Deiry
author_facet	Lindsey Carlsen Wafik S. El-Deiry
author_sort	Lindsey Carlsen
title	Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
title_short	Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
title_full	Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
title_fullStr	Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
title_full_unstemmed	Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
title_sort	differential p53-mediated cellular responses to dna-damaging therapeutic agents
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/63e53515f0ec4079b1faa8341d961d21
work_keys_str_mv	AT lindseycarlsen differentialp53mediatedcellularresponsestodnadamagingtherapeuticagents AT wafikseldeiry differentialp53mediatedcellularresponsestodnadamagingtherapeuticagents
_version_	1718432120468144128

Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents

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