p73 in Cancer
Bibliographic record
Abstract
p73 is a tumor suppressor belonging to the p53 family of transcription factors. Distinct isoforms are transcribed from the p73 locus. The use of 2 promoters at the N-terminus allows the expression of an isoform containing (TAp73) or not containing (ΔNp73) a complete N-terminal transactivation domain, with the latter isoform capable of a dominant negative effect over the former. In addition, both N-terminal variants are alternatively spliced at the C-terminus. TAp73 is a bona fide tumor suppressor, being able to induce cell death and cell cycle arrest; conversely, ΔNp73 shows oncogenic properties, inhibiting TAp73 and p53 functions. Here, we discuss the latest findings linking p73 to cancer. The generation of isoform specific null mice has helped in dissecting the contribution of TA versus ΔNp73 isoforms to tumorigenesis. The activity of both isoforms is regulated transcriptionally and by posttranslational modification. p73 dysfunction, particularly of TAp73, has been associated with mitotic abnormalities, which may lead to polyploidy and aneuploidy and thus contribute to tumorigenesis. Although p73 is only rarely mutated in cancer, the tumor suppressor actions of TAp73 are inhibited by mutant p53, a finding that has important implications for cancer therapy. Finally, we discuss the expression and role of p73 isoforms in human cancer, with a particular emphasis on the neuroblastoma cancer model. Broadly, the data support the hypothesis that the ratio between TAp73 and ΔNp73 is crucial for tumor progression and therapeutic response.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.012 | 0.008 |
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".