Mechanisms used by p73, p63 and XIAP to regulate survival and apoptosis of sympathetic neurons
Bibliographic record
Abstract
Developmental neuron death is determined by the activities of pro-survival and pro-apoptotic proteins. Here, we investigate the functions of three such proteins---p73, p63 and XIAP---in cultured neonatal sympathetic neurons. p73 and p63 are members of the p53 family that exist in both full-length (TA) and truncated (DeltaN) isoforms. First, we ask whether DeltaNp73 mediates sympathetic neuron survival in p53-dependent and/or -independent fashions. Overexpression of DeltaNp73 in sympathetic neurons withdrawn from NGF prevents upregulation of the p53 targets p21waf1 and Apaf-1, induction of the BH3-only protein BimEL, and cleavage of the effector caspase-3. DeltaNp73 also promotes survival in p53-independent manner by acting upstream of p53 to decrease JNK phosphorylation. Second, we ask whether p63 functions as a pro-apoptotic molecule in a manner similar to that of p53. TAp63 levels markedly increase in sympathetic neurons withdrawn from NGF. Similar to p53, TAp63 overexpression in neurons maintained in NGF upregulates p21waf1 and Apaf-1 levels, induces caspase-3 cleavage, and does not induce BimEL levels and JNK phosphorylation. Third, we examine the role of the caspase inhibitor XIAP and ask whether XIAP is a substrate of the serine/threonine kinase Akt. XIAP rescues NGF withdrawal- and LY294002-induced apoptosis and promotes sympathetic neuron survival cooperatively with Ras. In addition, Akt associates with XIAP and phosphorylates XIAP at serine 87.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".