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Vol. 273, Issue 4, 2008-2014, January 23, 1998
From the Department of Molecular and Cell Biology and The Cancer
Research Laboratory, University of California,
Berkeley, California 94720
The preceding paper (Cha, H. H., Cram,
E. J., Wang, E. C., Huang, A. J., Kasler, H. G.,
and Firestone, G. L. (1998) J. Biol. Chem. 273, 0000-0000(478563) defined a glucocorticoid responsive region within
the promoter of the p21 CDK inhibitor gene that contains a putative
DNA-binding site for the transcription factor CCAAT/enhancer binding
protein-
Role of the CCAAT/Enhancer Binding Protein-
Transcription
Factor in the Glucocorticoid Stimulation of p21waf1/cip1 Gene
Promoter Activity in Growth-arrested Rat Hepatoma Cells
(C/EBP). Wild type rat BDS1 hepatoma cells as well as
as4 hepatoma cells, which express antisense sequences to C/EBP and
ablate its protein production, were utilized to investigate the role of
this transcription factor in the glucocorticoid regulation of p21 gene
expression. The stimulation of p21 protein levels and promoter
activity, as well as inhibition of CDK2-mediated retinoblastoma protein
phosphorylation, by the synthetic glucocorticoid, dexamethasone,
required the expression of C/EBP. Overexpression of C/EBP in as4
cells rescued the dexamethasone responsiveness of the p21 promoter.
Site-directed mutagenesis of the p21 promoter revealed that
dexamethasone stimulation of p21 promoter activity required
the C/EBP consensus DNA-binding site. Furthermore, in glucocorticoid receptor-defective EDR1 hepatoma cells, dexamethasone failed to stimulate C/EBP and p21 protein expression and promoter activities. Our results have established a functional link between the
glucocorticoid receptor signaling pathway that mediates a G1 cell cycle arrest of rat hepatoma cells and the
transcriptional control of p21 by a cascade that requires the steroid
induction of C/EBP gene expression.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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S. Hong, S. J. Park, H. J. Kong, J. D. Shuman, and J. Cheong Functional Interaction of bZIP Proteins and the Large Subunit of Replication Factor C in Liver and Adipose Cells J. Biol. Chem., July 20, 2001; 276(30): 28098 - 28105. [Abstract] [Full Text] [PDF]
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