p53-mediated redox control promotes liver regeneration and maintains liver function in  response to CCl4

Timothy J Humpton; Holly Hall; Christos Kiourtis; Colin Nixon; William Clark; Ann Hedley; Robin Shaw; Thomas G Bird; Karen Blyth; Karen H. Vousden

doi:10.1038/s41418-021-00871-3

p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl4

Timothy J Humpton^*, Holly Hall, Christos Kiourtis, Colin Nixon, William Clark, Ann Hedley, Robin Shaw, Thomas G Bird, Karen Blyth, Karen H. Vousden^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 the 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 (CCl4). Here, we show that p53 functions to support repair and recovery from CCl4-mediated liver damage, control reactive oxygen species (ROS) and limit 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.

Original language	English
Journal	Cell Death & Differentiation (CDD)
Early online date	9 Oct 2021
DOIs	https://doi.org/10.1038/s41418-021-00871-3
Publication status	E-pub ahead of print - 9 Oct 2021

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s41418-021-00871-3
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title = "p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl4",

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 the 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 (CCl4). Here, we show that p53 functions to support repair and recovery from CCl4-mediated liver damage, control reactive oxygen species (ROS) and limit 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.",

author = "Humpton, {Timothy J} and Holly Hall and Christos Kiourtis and Colin Nixon and William Clark and Ann Hedley and Robin Shaw and Bird, {Thomas G} and Karen Blyth and Vousden, {Karen H.}",

year = "2021",

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doi = "10.1038/s41418-021-00871-3",

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T1 - p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl4

AU - Humpton, Timothy J

AU - Hall, Holly

AU - Kiourtis, Christos

AU - Nixon, Colin

AU - Clark, William

AU - Hedley, Ann

AU - Shaw, Robin

AU - Bird, Thomas G

AU - Blyth, Karen

AU - Vousden, Karen H.

PY - 2021/10/9

Y1 - 2021/10/9

N2 - 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 the 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 (CCl4). Here, we show that p53 functions to support repair and recovery from CCl4-mediated liver damage, control reactive oxygen species (ROS) and limit 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.

AB - 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 the 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 (CCl4). Here, we show that p53 functions to support repair and recovery from CCl4-mediated liver damage, control reactive oxygen species (ROS) and limit 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.

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DO - 10.1038/s41418-021-00871-3

M3 - Article

SN - 1350-9047

JO - Cell Death & Differentiation (CDD)

JF - Cell Death & Differentiation (CDD)

ER -

p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl4

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