Identification of a Co-repressor That Inhibits the Transcriptional and Growth-Arrest Activities of CCAAT/Enhancer-binding Protein α
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".