| First Author | McFie PJ | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 26 | Pages | 18069-80 |
| PubMed ID | 16644732 | Mgi Jnum | J:114355 |
| Mgi Id | MGI:3688812 | Doi | 10.1074/jbc.M512734200 |
| Citation | McFie PJ, et al. (2006) Identification of a co-repressor that inhibits the transcriptional and growth-arrest activities of CCAAT/enhancer-binding protein alpha. J Biol Chem 281(26):18069-80 |
| abstractText | 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. |
