P53 and BCL-2 family proteins PUMA and NOXA define competitive fitness in pluripotent cell competition.
PLoS Genet
; 20(3): e1011193, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38489392
ABSTRACT
Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cells in vitro and in vivo. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell Competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína p53 Supresora de Tumor
/
Proteínas Proto-Oncogénicas c-bcl-2
/
Competencia Celular
Límite:
Animals
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
España