Involvement of the cell-cycle inhibitor Cip1/WAF1 and the E1A-associated p300 protein in terminal differentiation.
Détails
ID Serval
serval:BIB_962ABB999F83
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Involvement of the cell-cycle inhibitor Cip1/WAF1 and the E1A-associated p300 protein in terminal differentiation.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
1995
Volume
92
Numéro
12
Pages
5451-5455
Langue
anglais
Résumé
The mechanism of cell cycle withdrawal during terminal differentiation is poorly understood. We report here that the cyclin-dependent kinase (CDK) inhibitor p21Cip1/WAF1 is induced at early times of both keratinocyte and myoblast differentiation. p21Cip1/WAF1 induction is accompanied by a drastic inhibition of total Cdk2, as well as p21Cip1/WAF1-associated CDK kinase activities. p21Cip1/WAF1 has been implicated in p53-mediated G1 arrest and apoptosis. In keratinocyte differentiation, Cip1/WAF1 induction is observed even in cells derived from p53-null mice. Similarly, keratinocyte differentiation is associated with induction of Cip1/WAF1 promoter activity in both wild-type and p53-negative keratinocytes. Induction of the Cip1/WAF1 promoter upon differentiation is abolished by expression of an adenovirus E1A oncoprotein (d1922/947), which is unable to bind p105-Rb, p107, or cyclin A but which still binds the nuclear phosphoprotein p300. Overexpression of p300 can suppress the E1A effect, independent of its direct binding to E1A. Thus, terminal differentiation-induced growth arrest in both keratinocyte and myoblast systems is associated with induction of Cip1/WAF1 expression. During keratinocyte differentiation, Cip1/WAF1 induction does not require p53 but depends on the transcriptional modulator p300.
Mots-clé
Animals, Cell Differentiation/genetics, Cell Differentiation/physiology, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/genetics, Cyclins/physiology, E1A-Associated p300 Protein, Gene Expression Regulation, Genes, p53, Keratinocytes/cytology, Keratinocytes/metabolism, Mice, Mice, Inbred SENCAR, Muscles/cytology, Muscles/metabolism, Nuclear Proteins/physiology, Protein Kinase Inhibitors, Trans-Activators, Transcription Factors/physiology, Transcription, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:59
Dernière modification de la notice
20/08/2019 15:58