Lysine 63-linked ubiquitination is important for arachidonic acid-induced cellular adhesion and migration
Bibliographic record
Abstract
Arachidonic acid, a dietary cis-polyunsaturated fatty acid, stimulates adhesion and migration of human cancer cells on the extracellular matrix by activation of intracellular signaling pathways. Polyubiquitin chains bearing linkages through different lysine residues convey distinct structural and functional information that is important for signal transduction. We investigated whether ubiquitination was required for arachidonic acid-induced cellular adhesion and migration of MDA-MB-435 cells on collagen type IV. An E1 (ubiquitin-activating enzyme) inhibitor, PYR-431, completely abrogated arachidonic acid-stimulated adhesion. Additionally, expression of a lysine null mutant ubiquitin prevented activation of cellular adhesion. Cells expressing ubiquitin in which lysine 63 (K63) was mutated to arginine (K63R) were unable to adhere to collagen upon exposure to arachidonic acid. When K63 was the only lysine present, the cells retained the ability to adhere, indicating that K63-linked ubiquitin is both necessary and sufficient. Moreover, K63-linked ubiquitin was required for the induction of cell migration by arachidonic acid. The ubiquitin mutants and PYR-431 did not prevent arachidonic acid-induced phosphorylation of TGF-β activated kinase-1 (TAK1) and p38 MAPK, suggesting K63-linked ubiquitination occurs downstream of MAPK. These novel findings are the first to demonstrate a role for K63-linked ubiquitination in promoting cell adhesion and migration.
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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) | 0.001 | 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".