SLP-76 Adaptor Binding to SUMO-RANGAP1 of the Nuclear Pore Complex Regulates Multiple Aspects of T-cell Immunity
Bibliographic record
Abstract
Abstract While immune cell adaptors regulate various proximal events in T cell signaling, the direct regulation of the nuclear pore complex (NPC) has not been reported. On the cytoplasmic side of the NPC, there are cytoplasmic filaments composed of two fundamental proteins RanGAP1 and RanBP2. We previously showed that the immune cell adaptor SLP-76 binds directly to SUMO-RanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T cells (Liu et al., 2015 Mol Cell 59, 840–9). The use of a mutant form of SLP-76 that is unable to bind to RanGAP1 (i.e. K56E) reduced nuclear entry and T-cell cytokine production by >60%. It represents the second step in NFATc1 entry into the nucleus of T-cells following classic NFATc de-phosphorylation by calcineurin. We now show that K56E mutant reduced toll-like receptor induction of NF-κB nuclear entry (innate signaling) and that T-cells from K56E mutant mice show major defects in T-cell proliferation and immunity. Our findings further underscore the importance of this direct regulation of NPC function in T cell function.
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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 | 0.001 |
| 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".