Regulation of the Human Cyclin-dependent Kinase Inhibitor p18 by the Transcription Factors E2F1 and Sp1
Bibliographic record
Abstract
The p18(INK4c) cyclin-dependent kinase inhibitor is an important regulator of cell cycle progression and cellular differentiation. We and others found that overexpressed E2F proteins up-regulate p18 expression. To better understand this phenomenon, we performed a functional analysis of the human p18 promoter. Deletion studies revealed that the E2F-responsive elements of the promoter are located within 131 bp upstream of the transcription start site. This region contains putative Sp1- and E2F-binding sites. Mutational inactivation of these elements revealed that the Sp1 sites were important for the basal activity of the promoter but could also mediate the effects of E2F1 on the p18 promoter. Moreover, we found that E2F1 and Sp1 can synergistically enhance the activity of the proximal p18 promoter. Gel shift analyses using p18 promoter-derived probes led to the identification of several multiprotein complexes that were found to contain different combinations of E2F proteins and/or Sp1. Recombinant E2F1 was also capable of binding to the E2F-binding sites. Chromatin immunoprecipitation experiments demonstrated that E2F1 and E2F4 associate with the p18 promoter in unperturbed cells. Based on these findings, we conclude that E2F proteins and Sp1 play an important role in the control of p18 expression.
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".