New Regulators of Drug Sensitivity in the Family of Yeast Zinc Cluster Proteins
Bibliographic record
Abstract
The Gal4p family of yeast zinc cluster proteins comprises over 50 members that are putative transcriptional regulators. For example, Pdr1p and Pdr3p activate multidrug resistance genes by binding to pleiotropic drug response elements (PDREs) found in promoters of target genes such as PDR5, encoding a drug efflux pump involved in resistance to cycloheximide. However, the role of many zinc cluster proteins is unknown. We tested a panel of strains carrying deletions of zinc cluster genes in the presence of various drugs. One deletion strain (Deltardr1) was resistant to cycloheximide, whereas eight strains showed sensitivity to the antifungal ketoconazole or cycloheximide. Unnamed zinc cluster genes identified in our screen were called RDS for regulators of drug sensitivity. RNA levels of multidrug resistance genes such as PDR16, SNQ2, and PDR5 were decreased in many deletion strains. For example, cycloheximide sensitivity of a Deltastb5 strain was correlated with decreased RNA levels and promoter activity of the PDR5 gene. We tested if activation of PDR5 is mediated via a PDRE by inserting this DNA element in front of a minimal promoter linked to the lacZ gene. Strikingly, activity of the reporter was decreased in a Deltastb5 strain. The purified DNA binding domain of Stb5p bound to a PDRE in vitro. Mutations in the PDRE known to affect binding of Pdr1p/Pdr3p showed similar effects when assayed with Stb5p. These results strongly suggest that Stb5p is a transcriptional activator of multidrug resistance genes. Thus, we have identified new regulators of drug sensitivity in the family of zinc cluster proteins.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".