Back to Search
Start Over
p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2003 Jul; Vol. 23 (13), pp. 4713-27. - Publication Year :
- 2003
-
Abstract
- The p53 and NF-kappaB transcription factor families are important, multifunctional regulators of the cellular response to stress. Here we have investigated the regulatory mechanisms controlling p53-dependent cell cycle arrest and cross talk with NF-kappaB. Upon induction of p53 in H1299 or U-2 OS cells, we observed specific repression of cyclin D1 promoter activity, correlating with a decrease in cyclin D1 protein and mRNA levels. This repression was dependent on the proximal NF-kappaB binding site of the cyclin D1 promoter, which has been shown to bind the p52 NF-kappaB subunit. p53 inhibited the expression of Bcl-3 protein, a member of the IkappaB family that functions as a transcriptional coactivator for p52 NF-kappaB and also reduced p52/Bcl-3 complex levels. Concomitant with this, p53 induced a significant increase in the association of p52 and histone deacetylase 1 (HDAC1). Importantly, p53-mediated suppression of the cyclin D1 promoter was reversed by coexpression of Bcl-3 and inhibition of p52 or deacetylase activity. p53 therefore induces a transcriptional switch in which p52/Bcl-3 activator complexes are replaced by p52/HDAC1 repressor complexes, resulting in active repression of cyclin D1 transcription. These results reveal a unique mechanism by which p53 regulates NF-kappaB function and cell cycle progression.
- Subjects :
- B-Cell Lymphoma 3 Protein
Cell Cycle
Cell Line
Cyclin D1 genetics
Flow Cytometry
Genes, Reporter
Histone Deacetylase 1
Humans
Immunoblotting
Models, Biological
Models, Genetic
Plasmids metabolism
Precipitin Tests
Promoter Regions, Genetic
Protein Binding
RNA metabolism
RNA pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Serine metabolism
Time Factors
Transcription Factors
Transfection
Tumor Cells, Cultured
Ultraviolet Rays
Cyclin D1 metabolism
Down-Regulation
Histone Deacetylases metabolism
NF-kappa B metabolism
Proto-Oncogene Proteins metabolism
Transcription, Genetic
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 23
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 12808109
- Full Text :
- https://doi.org/10.1128/MCB.23.13.4713-4727.2003