p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen.
J Cell Biol
; 219(11)2020 11 02.
Article
em En
| MEDLINE
| ID: mdl-32886745
ABSTRACT
The mechanisms by which TP53, the most frequently mutated gene in human cancer, suppresses tumorigenesis remain unclear. p53 modulates various cellular processes, such as apoptosis and proliferation, which has led to distinct cellular mechanisms being proposed for p53-mediated tumor suppression in different contexts. Here, we asked whether during tumor suppression p53 might instead regulate a wide range of cellular processes. Analysis of mouse and human oncogene-expressing wild-type and p53-deficient cells in physiological oxygen conditions revealed that p53 loss concurrently impacts numerous distinct cellular processes, including apoptosis, genome stabilization, DNA repair, metabolism, migration, and invasion. Notably, some phenotypes were uncovered only in physiological oxygen. Transcriptomic analysis in this setting highlighted underappreciated functions modulated by p53, including actin dynamics. Collectively, these results suggest that p53 simultaneously governs diverse cellular processes during transformation suppression, an aspect of p53 function that would provide a clear rationale for its frequent inactivation in human cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Transformação Celular Neoplásica
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Proteína Supressora de Tumor p53
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Senescência Celular
/
Apoptose
/
Reparo do DNA
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá