AuroraB-kinase methylation by SETD6 regulates cytokinesis and protects cells from chromosomal instability
Bibliographic record
Abstract
ABSTRACT SETD6 is a non-histone lysine methylatransferase, previously shown to participate in several housekeeping signaling pathways such as the NFkB pathway, Wnt signaling pathway, mitosis and more. In the current study we show evidence that SETD6 methylation is involved in the regulation of cytokinesis - the final process that divides cell contents into two daughter cells. SETD6 depleted HeLa cells presented high levels of chromatin bridges and actin patches, which are commonly observed following chromosomal segregation errors. In a proteomic screen we identified Aurora-B as a novel SETD6 substrate. Aurora-B kinase is an essential regulator of cytokinesis, known to actively delay cytokinesis as a response to the presence of chromatin in the midzone. We found that SETD6 binds and methylates Aurora-B on two adjacent lysine residues. Upon replication stress, Aurora-B methylation by SETD6 increases but is abolished when the two lysine methylation targets are substituted. In addition, replication stress led to a high tendency of SETD6 depleted cells to multinucleate, a major chromosomal-instability (CIN) phenotype. We detected a significant reduction in the Aurora-B kinase activity during cytokinesis in SETD6 knockout cells upon replication stress, which could be the mechanism underlying the accumulation of CIN phenotypes in these cells. CIN is a hallmark of cancer and is associated with tumor cell malignancy. Our findings suggest that Aurora-B methylation by SETD6 carries meaningful implications on tumorigenic cellular pathways.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".