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p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl4.
Humpton, Timothy J; Hall, Holly; Kiourtis, Christos; Nixon, Colin; Clark, William; Hedley, Ann; Shaw, Robin; Bird, Thomas G; Blyth, Karen; Vousden, Karen H.
Afiliação
  • Humpton TJ; The Francis Crick Institute, London, NW1 1AT, UK. tim.humpton@crick.ac.uk.
  • Hall H; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. tim.humpton@crick.ac.uk.
  • Kiourtis C; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Nixon C; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Clark W; Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
  • Hedley A; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Shaw R; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Bird TG; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Blyth K; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
  • Vousden KH; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Cell Death Differ ; 29(3): 514-526, 2022 03.
Article em En | MEDLINE | ID: mdl-34628485
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 (CCl4). Here, we show that p53 functions to support repair and recovery from CCl4-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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article