Mouse models to investigate in situ cell fate decisions induced by p53

Lieschke, E; Thomas, AF; Kueh, A; Atkin-Smith, GK; Baldoni, PL; La Marca, JE; Young, S; Huang, AS; Ross, AM; Whelan, L; Kaloni, D; Tai, L; Smyth, GK; Herold, MJ; Hawkins, ED; Strasser, A; Kelly, GL

Author(s): Lieschke, E; Thomas, AF; Kueh, A; Atkin-Smith, GK; Baldoni, PL; La Marca, JE; Young, S; Huang, AS; Ross, AM; Whelan, L; Kaloni, D; Tai, L; Smyth, GK; Herold, MJ; Hawkins, ED; Strasser, A; Kelly, GL;
Details: Publication Year 2024-08-19,Volume 43,Issue #19,Page 4406-4436
Journal Title: EMBO Journal
Abstract: Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. Also, the context-dependent interaction partners and binding loci of p53 remain largely elusive. To be able to examine these questions, we here developed knock-in mice expressing triple-FLAG-tagged p53 to facilitate p53 pull-down and two p53 response reporter mice, knocking tdTomato and GFP into the Puma/Bbc3 and p21 gene loci, respectively. By crossing these reporter mice into a p53-deficient background, we show that the new reporters reliably inform on p53-dependent and p53-independent initiation of both apoptotic or cell cycle arrest/senescence programs, respectively, in vitro and in vivo.
Publisher: EMBO Press
Keywords: Apoptosis; Cancer; Cell Cycle Arrest; Reporter Mice; p53/TRP53/TP53
Research Division(s): Blood Cells And Blood Cancer; Inflammation; Bioinformatics
PubMed ID: 39160273
Publisher's Version: https://doi.org/10.1038/s44318-024-00189-z
Open Access at Publisher's Site: https://doi.org/ 10.1038/s44318-024-00189-z
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-23 02:54:09

Last Modified: 2024-10-03 09:19:51