Glutathione Transferase P1 (GSTP1) is Modified by Palmitate
Bibliographic record
Abstract
Glutathione transferase P1 (GSTP1) protects cells from carcinogens by catalyzing their conjugation with the tripeptide glutathione (γ‐Glu‐Cys‐Gly). GSTP1 is also involved in cell signaling, proliferation and apoptosis. Overexpression of GSTP1 in tumors and single nucleotide polymorphic variants are associated with anti‐cancer drug resistance and poor prognosis. In contrast, inactivation of GSTP1 due to epigenetic promoter silencing increases susceptibility to certain cancer types, with prostate cancer as the best studied example. GSTP1 is classically described as a cytosolic enzyme; however, we have reported that it is strongly associated with the plasma membrane and the strength is comparable to the integral membrane protein Na + /K + ‐ATPase. We hypothesize that the addition of a hydrophobic component is required to allow its strong interaction with membranes. Palmitoylation is the reversible post‐translational addition of a 16‐C saturated fatty acid to proteins, most commonly on Cys residues through a thioester bond. We found that GSTP1 is modified by palmitate. However, Cys‐less (Cys to Ser or Cys to Ala) mutants expressed in MCF7 cells surprisingly retained palmitoylation. In addition, treatment of palmitoylated GSTP1 with NaOH, which cleaves thioester bonds, did not remove palmitate. These data suggested that GSTP1 is modified by palmitate on at least one non‐Cys residue. We also demonstrated that GSTP1 can be non‐catalytically palmitoylated (or autoplamitoylated). Peptide sequencing by ESI‐MS/MS of the autopalmitoylated GSTP1 revealed that Cys48 and Cys102 undergo S‐ palmitoylation and Lys103 undergoes N‐ palmitoylation. N ‐palmitoylation of an internal Lys residue is a rare observation and provides an explanation for the resistance of GSTP1 palmitoylation to NaOH treatment. In conclusion, we have identified palmitoylation as a novel post‐translational modification of GSTP1. This research lays the foundation for understanding the fundamental biology of GSTP1 and how palmitoylation may influence its structure, function and membrane association. Support or Funding Information Canadian Institute of Health Research (CIHR), Alberta Innovates Health Solutions (AIHS) and Alberta Cancer Foundation (ACF)
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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 | 0.000 | 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) | 0.000 | 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".