Identification of a Co-repressor That Inhibits the Transcriptional and Growth-arrest Activities of Ccaat/Enhancer-binding Protein Alpha.
From: Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
The Journal of biological chemistry
- Publish Date: Jun 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 26
- Pages: 18069-80
- Medium: Print
- Language: English
- Citation (JAMA): McFie Pamela J, Wang Guo-Li, Timchenko Nicholai A, et al. Identification of a Co-repressor That Inhibits the Transcriptional and Growth-arrest Activities of Ccaat/Enhancer-binding Protein Alpha.. J. Biol. Chem. Jun 2006;281:18069-80
Abstract
We used a yeast two-hybrid screening approach to identify novel interactors of CCAAT/enhancer-binding protein alpha (C/EBPalpha) that may offer insight into its mechanism of action and regulation. One clone obtained was that for CA150, a nuclear protein previously characterized as a transcriptional elongation factor. In this report, we show that CA150 is a widely expressed co-repressor of C/EBP proteins. Two-hybrid and co-immunoprecipitation analyses indicated that CA150 interacts with C/EBPalpha. Overexpression of CA150 inhibited the transactivation produced by C/EBPalpha and was also able to reverse the enhancing effect of the co-activator p300 on C/EBPbeta-mediated transactivation. Analysis of C/EBPalpha mutants indicated that CA150 interacts with C/EBPalpha primarily through a domain spanning amino acids 135-150. Chromatin immunoprecipitation assays showed that CA150 was present on a promoter that is repressed by C/EBPalpha but not present on a promoter that is activated by C/EBPalpha. Finally, we showed that in cells in which growth arrest had been induced by ectopic expression of C/EBPalpha, CA150 was able to release them from growth arrest. Interestingly, CA150 could not reverse the growth arrest produced by the minimal growth-arrest domain of C/EBPalpha (amino acids 175-217), suggesting that the effect of CA150 was directed at a region of C/EBPalpha outside of this minimal domain, consistent with our two-hybrid analysis. Taken together, these data indicate that CA150 is a co-repressor of C/EBP proteins and provides a possible mechanism for how C/EBPalpha can repress transcription of specific genes.
Mesh Headings (Keywords): Animals, CCAAT-Enhancer-Binding Protein-alpha, COS Cells, Carcinoma, Hepatocellular, Cell Division, Cell Line, Tumor, Cercopithecus aethiops, Gene Library, Humans, Liver Neoplasms, Repressor Proteins, Trans-Activators, Transcription, Genetic, Transfection, Two-Hybrid System Techniques
Check for Full Text / PubMed Unique Identifier (PMID): 16644732
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