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Developmental Acquisition of p53 Functions
Version 1
: Received: 14 October 2021 / Approved: 18 October 2021 / Online: 18 October 2021 (15:12:11 CEST)
A peer-reviewed article of this Preprint also exists.
Jaiswal, S.K.; Raj, S.; DePamphilis, M.L. Developmental Acquisition of P53 Functions. Genes 2021, 12, 1675, doi:10.3390/genes12111675. Jaiswal, S.K.; Raj, S.; DePamphilis, M.L. Developmental Acquisition of P53 Functions. Genes 2021, 12, 1675, doi:10.3390/genes12111675.
Abstract
Abstract: 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 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 p53‑dependent transcription is first detected in late mouse blastocysts, that p53 activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on p53. Furthermore, p53 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, p53 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 p53-independent. In embryonic fibroblasts, p53 induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.
Keywords
pluripotent; embryo; stem cells; genomic stability; cell cycle; apoptosis; differentiation; cancer
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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