Journal article
Mouse models to investigate in situ cell fate decisions induced by p53
E Lieschke, AF Thomas, A Kueh, GK Atkin-Smith, PL Baldoni, JE La Marca, S Young, AS Huang, AM Ross, L Whelan, D Kaloni, L Tai, GK Smyth, MJ Herold, ED Hawkins, A Strasser, GL Kelly
EMBO Journal | Published : 2024
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, ..
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Grants
Awarded by Australian Government
Funding Acknowledgements
We thank Drs Michael Milevskiy, Stephen Wilcox and Sarah MacRaild at WEHI for help with the CUT&RUN sequencing. We thank Dr Simon Monard, the WEHI flow cytometry core facility and the WEHI dynamic imaging department for advice about DNA content flow cytometry analysis, and microscopy. We thank the WEHI Bioservices Department, in particular Michael Watters, Dan Fayle, and Rebekah Meeny, for their excellent animal husbandry services. The generation of the FLAG-Trp53, p21-IRES-GFP and Puma-tdTomato mice used in this study was supported by Phenomics Australia and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) programme. This work was funded by the Australian National Health and Medical Research Council, NHMRC, (Fellowship 1154970 to GKS; Programme Grant GNT1113133 to AS, Research Fellowship GNT1116937 to AS, Project Grant GNT1143105 to AS, Ideas Grants GNT 2002618 and GNT2001201 to GLK, Synergy Grants GNT2011139 to GLK and GNT 2010275 to AS), the Victorian Cancer Agency (MCRF Fellowship 17028 to GLK), the Estate of Anthony (Toni) Redstone OAM (to AS and GLK), the Craig Perkins Cancer Research Foundation (to GLK), the Dyson Bequest (to GLK) and the Harry Secomb Foundation (to GLK), and operational infrastructure grants through the Victorian State Government Operational Infrastructure Support (OIS) and Australian Government NHMRC Independent Research Institute Infrastructure Support (IRIIS) Schemes.