Triap1 upregulation promotes escape from mitotic-slippage-induced G1 arrest.
Cell Rep
; 42(3): 112215, 2023 03 28.
Article
em En
| MEDLINE
| ID: mdl-36917609
ABSTRACT
Drugs targeting microtubules rely on the mitotic checkpoint to arrest cell proliferation. The prolonged mitotic arrest induced by such drugs is followed by a G1 arrest. Here, we follow for several weeks the fate of G1-arrested human cells after treatment with nocodazole. We find that a small fraction of cells escapes from the arrest and resumes proliferation. These escaping cells experience reduced DNA damage and p21 activation. Cells surviving treatment are enriched for anti-apoptotic proteins, including Triap1. Increasing Triap1 levels allows cells to survive the first treatment with reduced DNA damage and lower levels of p21; accordingly, decreasing Triap1 re-sensitizes cells to nocodazole. We show that Triap1 upregulation leads to the retention of cytochrome c in the mitochondria, opposing the partial activation of caspases caused by nocodazole. In summary, our results point to a potential role of Triap1 upregulation in the emergence of resistance to drugs that induce prolonged mitotic arrest.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Mitose
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2023
Tipo de documento:
Article