Developmental Acquisition of p53 Functions

Remarkably, the p53 transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify p53-dependent developmental events have produced contradictory conclusions. Given the importance of p...

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Autores principales:	Sushil K. Jaiswal, Sonam Raj, Melvin L. DePamphilis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pluripotent embryo stem cells genomic stability cell cycle apoptosis Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2793614d09db4530a419aa0c1ddf1fcf
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spelling	oai:doaj.org-article:2793614d09db4530a419aa0c1ddf1fcf2021-11-25T17:40:42ZDevelopmental Acquisition of <i>p53</i> Functions10.3390/genes121116752073-4425https://doaj.org/article/2793614d09db4530a419aa0c1ddf1fcf2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1675https://doaj.org/toc/2073-4425Remarkably, the <i>p53</i> transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify <i>p53</i>-dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that <i>p53</i>-dependent transcription is first detected in late mouse blastocysts, that <i>p53</i> activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on <i>p53</i>. Furthermore, <i>p53</i> does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, <i>p53</i> accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are <i>p53</i>-independent. In embryonic fibroblasts, <i>p53</i> induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.Sushil K. JaiswalSonam RajMelvin L. DePamphilisMDPI AGarticlepluripotentembryostem cellsgenomic stabilitycell cycleapoptosisGeneticsQH426-470ENGenes, Vol 12, Iss 1675, p 1675 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pluripotent embryo stem cells genomic stability cell cycle apoptosis Genetics QH426-470
spellingShingle	pluripotent embryo stem cells genomic stability cell cycle apoptosis Genetics QH426-470 Sushil K. Jaiswal Sonam Raj Melvin L. DePamphilis Developmental Acquisition of <i>p53</i> Functions
description	Remarkably, the <i>p53</i> transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify <i>p53</i>-dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that <i>p53</i>-dependent transcription is first detected in late mouse blastocysts, that <i>p53</i> activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on <i>p53</i>. Furthermore, <i>p53</i> does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, <i>p53</i> accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are <i>p53</i>-independent. In embryonic fibroblasts, <i>p53</i> induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.
format	article
author	Sushil K. Jaiswal Sonam Raj Melvin L. DePamphilis
author_facet	Sushil K. Jaiswal Sonam Raj Melvin L. DePamphilis
author_sort	Sushil K. Jaiswal
title	Developmental Acquisition of <i>p53</i> Functions
title_short	Developmental Acquisition of <i>p53</i> Functions
title_full	Developmental Acquisition of <i>p53</i> Functions
title_fullStr	Developmental Acquisition of <i>p53</i> Functions
title_full_unstemmed	Developmental Acquisition of <i>p53</i> Functions
title_sort	developmental acquisition of <i>p53</i> functions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2793614d09db4530a419aa0c1ddf1fcf
work_keys_str_mv	AT sushilkjaiswal developmentalacquisitionofip53ifunctions AT sonamraj developmentalacquisitionofip53ifunctions AT melvinldepamphilis developmentalacquisitionofip53ifunctions
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Developmental Acquisition of <i>p53</i> Functions

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