STAT3 Ser-727 phosphorylation by CDK1 inhibits STAT3 function during cell cycle progression
Bibliographic record
Abstract
5401 Using the Kinetworks(TM) KPSS 1.3 Phospho-Site Screening Service from Kinexus, we uncovered a 2- to 3-fold enhancement of the phosphorylation of the transcription factor STAT3 at Ser-727 in M-phase arrested HeLa cells exposed for 24 hours to various microtubule disruptors including nocodazole, taxol, vinblastine and colchicine. STAT3 Ser-727 phosphorylation was also increased during normal cell cycle progression through M phase, and this could be blocked with olomoucine, which is a cyclin-dependent kinase (CDK) inhibitor. CDK1 was shown to directly phosphorylate recombinant STAT3 at Ser-727 in vitro. In studies with STAT3 phosphorylation mutants transfected into HEK cells, the Ser-727 to Glu mutant exhibited reduced phosphorylation at the Tyr-705 activation site for transcription. Likewise, the Tyr-705 to Glu mutant had lower levels of Ser-727 phosphorylation. STAT3 Ser-727 to Ala mutants exhibited increased transcriptional activity with the STAT3 promoter in luciferase reporter assays and electrophoretic mobility shift assays that monitor DNA binding. DNA synthesis as measured by BrdU incorporation was increased in HEK cells transfected with the STAT3 Ser-727 to Ala mutant. The Kinetworks(TM) KCCP Cell Cycle Protein Screening Service revealed that the STAT3 Ser-727 to Ala mutant also enhanced the level of production of cyclin E and the p21 CDK inhibitor in HEK cells. STAT3 phosphorylation during M phase by CDK1 has not been previously described. We conclude that CDK1 and possibly CDK2 may phosphorylate STAT3 and inhibit its transcriptional activity during M phase and prior to S phase, respectively. [This work was supported by a Canada Institute for Health Research grant to SP].
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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) | 0.003 | 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".