Role of the CCAAT/Enhancer Binding Protein-α Transcription Factor in the Glucocorticoid Stimulation of p21 Gene Promoter Activity in Growth-arrested Rat Hepatoma Cells

• DOI: 10.1074/jbc.273.4.2008
• Publication Date: 2002-07-26T15:13:03Z
• Authors: Erin J. Cram; Ross A. Ramos; Edward C. Wang; Helen H. Cha; Yukihiro Nishio; Gary L. Firestone
• Keywords: Ccaat-enhancer-binding proteins; Transcription; Promoter activity

The preceding paper (Cha, H. H., Cram, E. J., Wang, C., Huang, A. Kasler, G., and Firestone, G. L. (1998) J. Biol. Chem. 273, 0000-0000(478563) defined a glucocorticoid responsive region within teh promoter of the p21 CDK inhibitor gene that contains putative DNA-binding site for transcription factor CCAAT/ enhancer binding protein-alpha (C/EBP alpha). Wild type rat BDS1 hepatoma cells as well as4 cells, which express antisense sequences to C/EBP alpha ablate its protein production, were utilized investigate role this in regulation expression. stimulation levels activity, inhibition CDK2-mediated retinoblastoma phosphorylation, by synthetic glucocorticoid, dexamethasone, required expression alpha. Overexpression rescued dexamethasone responsiveness promoter. Site-directed mutagenesis revealed activity consensus site. Furthermore, receptor-defective EDR1 failed stimulate activities. Our results have established functional link between receptor signaling pathway mediates G1 cell cycle arrest transcriptional control cascade requires steroid induction