The initiation of UV-induced G1 arrest in human cells is independent of the p53/p21/pRb pathway but can be attenuated through expression of the HPV E7 oncoprotein
Bibliographic record
Abstract
It is well established that the initiation of G(1) arrest in cultured cells exposed to ionizing radiation (IR) is fully dependent upon the p53/p21waf1/pRb signaling cascade. However, the extent to which this pathway regulates G(1) arrest following exposure to UV is less clear. Here we demonstrate that primary human fibroblasts from either skin or lung, in which p53 has been functionally inactivated through expression of the human papillomavirus E6 oncoprotein, each undergoes a prolonged G(1) arrest upon UV irradiation. This same phenomenon is also observed for UV-exposed human tumor cell strains that are genetically deficient for p53, p21waf1 and/or pRb. Furthermore, for the isogenic wild-type counterparts of these primary and tumor cell strains, the onset of UV-induced G(1) arrest precedes any increase in the ratio of hypo- to hyper-phosphorylated pRb and virtually the entire period of growth arrest occurs in the absence of p21waf1 induction. The above data on UV-treated cells are in contrast to the expected situation for IR, for which G(1) arrest is abolished in all deficient cell lines, and, in the wild-type counterparts, correlates precisely with p21waf1 induction and an increase in the ratio of hypo- to hyper-phosphorylated pRb. Remarkably, it was observed that both IR- and UV-induced G(1) arrest are significantly attenuated in primary fibroblasts expressing the human papillomavirus E7 oncoprotein, which functionally inactivates pRb in addition to many other cellular proteins. Our findings conclusively demonstrate that the p53/p21/pRb cascade is not essential for the initiation of G(1) arrest in UV-exposed human cells and, furthermore, indicate the involvement in this process of any among a number of human papillomavirus E7-interacting cellular proteins.
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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) | 0.002 | 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".