G125A Single Nucleotide Polymorphism (SNP) in 5′-UTR of the Tumor Suppressor Gene Bax Affects Its Transcriptional Regulation.
Bibliographic record
Abstract
Abstract Lower expression of Bax protein in various human malignancies is associated with poor response to treatment and shorter disease-free survival. We (Cancer Lett2002; 187:199–205) and others (J Clin Oncol; 23:1514–21) have shown the association of a single nucleotide polymorphism (SNP) in the BAX promoter (G125A) with reduced protein expression and treatment resistance in chronic lymphocytic leukemia (CLL). Using luciferase reporter gene assay we demonstrated that this SNP significantly reduced BAX promoter activity (Oncogene2005; 24:2042–9). Our aim was to determine the effect of this polymorphism on the binding of transcription factors. For electrophoretic mobility shift (EMSA), HeLa and K562 nuclear extracts, and for chromatin immunoprecipitation (ChIP), K562 cells were used to study their ability to bind to a radiolabeled DNA probe corresponding to the BAX promoter region with G nucleotide at the position 125 or bearing G125A SNP. Super-shift assay was performed to determine the transcription factor involved in binding. Competition assays were performed to determine differences in the binding ability of the two probes. A panel of antibodies was tested by super-shift and ChIP assays, non-specific antibodies served as negative controls. Two major band shifts were detected by EMSA. The mobility of the detected complexes was different from those observed with GC1 probe, specific for Sp1/Sp3, suggesting the involvement of transcription factors other than Sp1/ Sp3. This was confirmed in super-shift assay and ChIP assay by incubating DNA probes with Sp1 or/ and Sp3 antibodies. We also found in the competition assays that the cold probes competed differently for binding. The findings provide evidence of the ability of G125A SNP to influence transcription factor binding in vitro (as shown in EMSA experiments) and in vivo (in ChIP experiments).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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".