puc
D. melanogaster
puckered
What the model saw
Gene: puc Organism: Drosophila melanogaster Known functions: puckered. JUN kinase phosphatase activity. MAP kinase tyrosine phosphatase activity. MAP kinase tyrosine/serine/threonine phosphatase activity. phosphoprotein phosphatase activity. protein binding. protein tyrosine phosphatase activity. protein tyrosine/threonine phosphatase activity.
View unredacted entry
puckered. JUN kinase phosphatase activity. MAP kinase tyrosine phosphatase activity. MAP kinase tyrosine/serine/threonine phosphatase activity. phosphoprotein phosphatase activity. protein binding. protein tyrosine phosphatase activity. protein tyrosine/threonine phosphatase activity.
Solver output
Puckered (puc) encodes a dual-specificity phosphatase that directly dephosphorylates and inactivates JNK (basket in Drosophila), acting as a negative feedback regulator of the JNK signaling pathway. Chronic or excessive JNK activation drives pro-inflammatory and pro-apoptotic transcriptional programs (via AP-1/dFos), promotes cellular senescence, and accelerates aging in Drosophila. By attenuating JNK signaling, puc suppresses these detrimental downstream effects. Loss of puc leads to hyperactivated JNK, increased oxidative stress responses gone awry, and tissue damage, while moderate JNK activity can be beneficial; however, puc's role as a brake on runaway JNK-driven inflammation and stress signaling places it firmly in the pro-longevity category. Studies in Drosophila have shown that fine-tuned JNK pathway activity (maintained partly by puc) is essential for normal lifespan, and overactivation of JNK through puc loss shortens lifespan.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity with 0.82 confidence, but the ground truth is anti_longevity. The model's mechanistic reasoning is partially correct in describing puc as a JNK phosphatase/negative regulator, but it draws the wrong conclusion about longevity influence. The key error is that puc is actually anti-longevity: JNK signaling in Drosophila is well-established as pro-longevity (activation of JNK extends lifespan), and puc as a negative regulator of JNK therefore suppresses longevity-promoting JNK activity. The model correctly identifies puc's role as a JNK inhibitor but incorrectly frames JNK hyperactivation as purely detrimental. In reality, JNK activation promotes stress resistance, autophagy, and longevity in Drosophila, so puc (which dampens JNK) is anti-longevity. The model's reasoning about 'runaway JNK-driven inflammation' shortening lifespan contradicts the established literature where JNK activation extends Drosophila lifespan. The model was highly confident in the wrong direction.
Raw API responses
solver
{
"reasoning": "Puckered (puc) encodes a dual-specificity phosphatase that directly dephosphorylates and inactivates JNK (basket in Drosophila), acting as a negative feedback regulator of the JNK signaling pathway. Chronic or excessive JNK activation drives pro-inflammatory and pro-apoptotic transcriptional programs (via AP-1/dFos), promotes cellular senescence, and accelerates aging in Drosophila. By attenuating JNK signaling, puc suppresses these detrimental downstream effects. Loss of puc leads to hyperactivated JNK, increased oxidative stress responses gone awry, and tissue damage, while moderate JNK activity can be beneficial; however, puc's role as a brake on runaway JNK-driven inflammation and stress signaling places it firmly in the pro-longevity category. Studies in Drosophila have shown that fine-tuned JNK pathway activity (maintained partly by puc) is essential for normal lifespan, and overactivation of JNK through puc loss shortens lifespan.",
"confidence": 0.82,
"key_pathways": [
"JNK/MAPK signaling pathway",
"AP-1 transcriptional regulation",
"stress-induced inflammation and apoptosis"
],
"mechanism_class": "chronic_inflammation",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.82 confidence, but the ground truth is anti_longevity. The model's mechanistic reasoning is partially correct in describing puc as a JNK phosphatase/negative regulator, but it draws the wrong conclusion about longevity influence. The key error is that puc is actually anti-longevity: JNK signaling in Drosophila is well-established as pro-longevity (activation of JNK extends lifespan), and puc as a negative regulator of JNK therefore suppresses longevity-promoting JNK activity. The model correctly identifies puc's role as a JNK inhibitor but incorrectly frames JNK hyperactivation as purely detrimental. In reality, JNK activation promotes stress resistance, autophagy, and longevity in Drosophila, so puc (which dampens JNK) is anti-longevity. The model's reasoning about 'runaway JNK-driven inflammation' shortening lifespan contradicts the established literature where JNK activation extends Drosophila lifespan. The model was highly confident in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}