CDK4-CDK6 inhibitors induce autophagy-mediated degradation of DNMT1 and facilitate the senescence antitumor response.
Autophagy
; 12(10): 1965-1966, 2016 10 02.
Article
em En
| MEDLINE
| ID: mdl-27532423
ABSTRACT
Senescence is a natural anticancer defense program disabled in tumor cells. We discovered that deregulated CDK4 (cyclin dependant kinase 4) and CDK6 activities contribute to senescence bypass during tumorigenesis and that their inhibition restores the senescence response in tumor cells. CDK4 and CDK6 phosphorylate RB1/RB, preventing its inhibitory interaction with the E2Fs, the cell cycle transcription factors. However, we also found that CDK4 interacts and phosphorylates the DNMT1 (DNA methyltransferase 1) protein protecting it from macroautophagy/autophagy-mediated protein degradation. This discovery highlights a new epigenetic component of CDK4-CDK6 signaling that could be exploited in cancer treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Senescência Celular
/
DNA (Citosina-5-)-Metiltransferases
/
Quinase 4 Dependente de Ciclina
/
Quinase 6 Dependente de Ciclina
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Proteólise
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Autophagy
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá