Humpton, T. J., Hall, H., Kiourtis, C. , Nixon, C., Clark, W., Hedley, A., Shaw, R., Bird, T. G., Blyth, K. and Vousden, K. H. (2022) p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl₄. Cell Death and Differentiation, 29(3), pp. 514-526. (doi: 10.1038/s41418-021-00871-3) (PMID:34628485) (PMCID:PMC8901761)
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Abstract
The p53 transcription factor coordinates wide-ranging responses to stress that contribute to its function as a tumour suppressor. The responses to p53 induction are complex and range from mediating the elimination of stressed or damaged cells to promoting survival and repair. These activities of p53 can modulate tumour development but may also play a role in pathological responses to stress such as tissue damage and repair. Using a p53 reporter mouse, we have previously detected strong induction of p53 activity in the liver of mice treated with the hepatotoxin carbon tetrachloride (CCl ). Here, we show that p53 functions to support repair and recovery from CCl -mediated liver damage, control reactive oxygen species (ROS) and limit the development of hepatocellular carcinoma (HCC), in part through the activation of a detoxification cytochrome P450, CYP2A5 (CYP2A6 in humans). Our work demonstrates an important role for p53-mediated redox control in facilitating the hepatic regenerative response after damage and identifies CYP2A5/CYP2A6 as a mediator of this pathway with potential prognostic utility in human HCC.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was funded by Cancer Research UK grant C596/A26855 and supported by The Francis Crick Institute which receives its core funding from Cancer Research UK (FC001557), the United Kingdom Medical Research Council (FC001557), and the Wellcome Trust (FC001557), and the CRUK Beatson Institute which receives its core funding from Cancer Research UK grant C596/A17196. HH was funded by BBSRC grant BB/N017005/2. Additional funding for the work was provided by Cancer Research UK grant A29799 (KB). TGB was funded by the Wellcome Trust (Grant number: WT107492Z) and CRUK HUNTER Accelerator Award (Grant number: A26813). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Blyth, Professor Karen and Clark, Mr William and Kiourtis, Christos and Bird, Dr Thomas and Nixon, Mr Colin and Vousden, Karen |
| Authors: | Humpton, T. J., Hall, H., Kiourtis, C., Nixon, C., Clark, W., Hedley, A., Shaw, R., Bird, T. G., Blyth, K., and Vousden, K. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cell Death and Differentiation |
| Publisher: | Springer Nature |
| ISSN: | 1350-9047 |
| ISSN (Online): | 1476-5403 |
| Published Online: | 09 October 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in Cell Death and Differentiation 29(3): 514-526 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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