Induction of WAF1/CIP1 by a p53-independent pathway.
Cancer Res
; 54(13): 3391-5, 1994 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-8012956
ABSTRACT
The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Fase G1
/
Genes Supressores de Tumor
/
Genes Precoces
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1994
Tipo de documento:
Article