SF-1 plays an essential role in the expression of the acth receptor gene in adrenal cells
Bibliographic record
Abstract
ACTH resistant mutant cells that fail to express the ACTH receptor (mc2r) were isolated. Fluctuation analysis indicated that these mutants likely originated from single mutational events. Analysis of the mutants showed that the mutation that leads to the impaired mc2r expression also compromises transcriptional activity of the proximal 1.8 Kb promoter of this gene. Limited deletion analysis of the promoter mapped the region between −106 and −13 as one involved in the differential activity of the promoter in parent Y1 and mutant cells, raising the possibility of impaired activity of the SF-1 site located at −25 bp. This hypothesis was further analyzed and results obtained further suggested that impaired SF-1 function played an important role in the mutant phenotype. Cotransfection of cells with a chimera of SF-1 and VP16 activation domain restored activity of the SF-1 responsive gene in the mutants. The DNA binding activity of SF-1 from mutants was assessed by analysis of electrophoretic mobility assays. The patterns of binding as well as the relative affinity observed were indistinguishable between parent and mutants. These results together with the SF-1/VP16 data suggest that an inability of SF-1 to activate transcription rather than impaired binding of SF-1 to DNA underlined the loss of ACTH receptor expression. Furthermore results from modified mammalian two hybrid assays indicated that the ability of SF-1 to recruit a prototype coactivator, GRIP1, was compromised in the mutants. Cloning and sequencing of SF-1 cDNA from parent and 10r6 mutants indicated the presence in the mutant of a missense mutation at position 514 bp (G to T) which causes an amino acid change (A172S). Southern analysis indicated that mutant cells are heterozygous for the mutant allele while parent cells are homozygous for the wild type SF-1. The Southern results further suggested that the mutant allele is amplified in the mutants. Cotransfection of parent cells with an SF-1 responsive reporter gene and an expression vector encoding the mutated SF-1 indicated that the mutated form is completely inactive. Furthermore, cotransfection of Y1 cells with the mutated and wild type SF-1 indicated that the mutation acted in a dominant negative fashion.
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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 | 0.001 |
| 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".