Repression of p15INK4b expression by Myc through association with Miz-1.
Nat Cell Biol
; 3(4): 392-9, 2001 Apr.
Article
em En
| MEDLINE
| ID: mdl-11283613
ABSTRACT
Deregulated expression of c-myc can induce cell proliferation in established cell lines and in primary mouse embryonic fibroblasts (MEFs), through a combination of both transcriptional activation and repression by Myc. Here we show that a Myc-associated transcription factor, Miz-1, arrests cells in G1 phase and inhibits cyclin D-associated kinase activity. Miz-1 upregulates expression of the cyclin-dependent kinases (CDK) inhibitor p15INK4b by binding to the initiator element of the p15INK4b promoter. Myc and Max form a complex with Miz-1 at the p15 initiator and inhibit transcriptional activation by Miz-1. Expression of Myc in primary cells inhibits the accumulation of p15INK4b that is associated with cellular senescence; conversely, deletion of c-myc in an established cell line activates p15INK4b expression. Alleles of c-myc that are unable to bind to Miz-1 fail to inhibit accumulation of p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Transporte
/
Proteínas Proto-Oncogênicas c-myc
/
Dedos de Zinco
/
Proteínas de Ciclo Celular
/
Inibidor p16 de Quinase Dependente de Ciclina
/
Proteínas Supressoras de Tumor
/
Proteínas de Ligação a DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Alemanha