Ubiquitination of the transcription factor c‐maf is mediated by multiple lysine residues (LB188)
Bibliographic record
Abstract
The transcription factor c‐MAF belongs to the family of basic leucine zipper transcription factors including c‐fos and c‐jun. Previous studies suggested that c‐Maf could be polyubiquitinated followed by degradation in the proteasomes, but the mechanism is not defined. Theoretically, any lysine residues in c‐MAF could be ubiquitinated. In the present study, we tried to find out the specific lysine residues mediating c‐MAF ubiquitination. Through a series of mutational screenings from lysine (K) to arginine (R), we found that any single lysine mutation (K to R) failed to prevent c‐MAF ubiquitination, and a single lysine residue failed to mediate c‐MAF ubiquitination, which indicated that multiple lysine residues were required for c‐MAF ubiquitination. Bioinformatics and computing analyses revealed that K85 and K350 could mediate c‐MAF ubiquitination, which was confirmed at the cell‐based assays. However, this duo was not the only pair because the K85R/K350R mutant could also be ubiquitinated. Functionally, both M12 (K85/K350) and W12 (K85R/K350R) mutants increased cyclin D2 promoter‐driven luciferase activity, but they were less potent than the lysine‐free counterpart (M14). Therefore, we demonstrated that c‐MAF ubiquitination is mediated by multiple lysine residues, of which K85 and K350 are sufficient but not the only duo in mediating the c‐MAF ubiquitination. Moreover, c‐MAF was found to be degraded by lysosomes. This study added a novel insight for c‐MAF functional modularity, suggesting that c‐MAF stability is strictly regulated. Grant Funding Source : National Natural Science Foundation of China
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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".