Requirements for cell cycle arrest by p16INK4a.
Mol Cell
; 6(3): 737-42, 2000 Sep.
Article
em En
| MEDLINE
| ID: mdl-11030353
ABSTRACT
Analysis of tumor-derived mutations has led to the suggestion that p16INK4a, cyclin D1, cdk4, and the retinoblastoma protein (pRB) are components of a regulatory pathway that is inactivated in most tumor cells. Cell cycle arrest induced by p16INK4a, an inhibitor of cyclin D-dependent kinases, requires pRB, and it has been proposed that this G1 arrest is mediated by pRB-E2F repressor complexes. By comparing the properties of primary mouse embryonic fibroblasts specifically lacking pRB-family members, we find that pRB is insufficient for a p16INK4a-induced arrest. In addition to pRB, a second function provided by either p107 or p130, two pRB-related proteins, is required for p16INK4a to block DNA synthesis. We infer that p16INK4a-induced arrest is not mediated exclusively by pRB, but depends on the nonredundant functions of at least two pRB-family members.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Proteínas de Transporte
/
Regulação Neoplásica da Expressão Gênica
/
Fase G1
/
Proteína do Retinoblastoma
/
Proteínas Proto-Oncogênicas
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article