Chemogenetic profiling of ubiquitin-like modifier pathways identifies NFATC2IP as a mediator of SUMO-dependent genome integrity
Bibliographic record
Abstract
Abstract The post-translational modification of proteins by ubiquitin and ubiquitin-like polypeptides controls multiple cellular processes including the abundance of a large fraction of the proteome. We applied genome-scale CRISPR/Cas9 screens to elucidate the genetic architecture of the response to inhibition of ubiquitin, NEDD8 and SUMO conjugation pathways as well as inhibition of the p97/VCP segregase. This effort identified 395 genes whose disruption alters the fitness of human cells when faced with perturbations in these pathways. We validated that the TMED2 and TMED10 proteins, which are localized to the secretory pathway, promote resistance to p97/VCP inhibition and also characterized NFATC2IP, an evolutionarily conserved protein harboring SUMO-like domains as a major player in promoting genomic integrity when SUMOylation is inhibited. We propose that NFATC2IP acts in interphase cells to promote the SUMO-dependent E3 ligase activity of the SMC5/SMC6 complex, which is critical for SUMO-dependent genome integrity.
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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".