Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

At a Crossroads to Cancer: How p53-induced Cell Fate Decisions Secure Genome Integrity

Version 1 : Received: 2 September 2021 / Approved: 3 September 2021 / Online: 3 September 2021 (13:13:48 CEST)

A peer-reviewed article of this Preprint also exists.

Rizzotto, D.; Englmaier, L.; Villunger, A. At a Crossroads to Cancer: How p53-Induced Cell Fate Decisions Secure Genome Integrity. Int. J. Mol. Sci. 2021, 22, 10883. Rizzotto, D.; Englmaier, L.; Villunger, A. At a Crossroads to Cancer: How p53-Induced Cell Fate Decisions Secure Genome Integrity. Int. J. Mol. Sci. 2021, 22, 10883.

Journal reference: Int. J. Mol. Sci. 2021, 22, 10883
DOI: 10.3390/ijms221910883

Abstract

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

Keywords

p53; genomic stability; cell death

Subject

LIFE SCIENCES, Cell & Developmental Biology

Comments (1)

Comment 1
Received: 10 September 2021
Commenter: Alberto Gandarillas
The commenter has declared there is no conflict of interests.
Comment: Congratulations for the work. Please note that p53 also maintains the keratinocyte proliferative potential of human keratinocytes, and when silenced, cells undergo terminal differentiation by mitotic slippage (Freije et al. Inactivation of p53 in Human Keratinocytes Leads to Squamous Differentiation and Shedding via Replication Stress and Mitotic Slippage. Cell Reports, 2014, https://doi.org/10.1016/j.celrep.2014.10.012).
Thanks,
Alberto Gandarillas.
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