cst-1
C. elegans
Serine/threonine-protein kinase cst-1 37kDa subunit
What the model saw
Gene: cst-1 Organism: Caenorhabditis elegans Known functions: Serine/threonine-protein kinase cst-1 37kDa subunit. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Serine/threonine-protein kinase cst-1 37kDa subunit. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
CST-1 is the C. elegans ortholog of mammalian STE20-like kinase (MST1/2), the core kinase of the Hippo signaling pathway. As a serine/threonine protein kinase, CST-1 phosphorylates and activates DAF-16 (FOXO transcription factor) directly, independently of the canonical insulin/IGF-1 signaling pathway. Activation of DAF-16 by CST-1 promotes expression of stress-resistance and longevity genes, and overexpression of cst-1 has been shown to extend lifespan in C. elegans. This places CST-1 as a positive regulator of the FOXO/DAF-16 axis, a central node in nutrient-sensing and longevity regulation. The kinase activity and ATP-binding function are the molecular basis for this phosphorylation-driven pro-longevity signaling.
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 correctly predicted cst-1 as pro_longevity with high confidence (0.82). The mechanistic reasoning is accurate: CST-1 is indeed the C. elegans ortholog of MST1/2 (mammalian STE20-like kinase), a core Hippo pathway kinase that directly phosphorylates and activates DAF-16/FOXO independently of the canonical IIS pathway, thereby promoting longevity. The model correctly identifies overexpression of cst-1 as extending lifespan. The mechanism class of "deregulated_nutrient_sensing" is a reasonable categorization given the DAF-16/FOXO connection, though "stress_response" or "Hippo signaling" might be more precise. Overall, the prediction and reasoning are well-supported by the literature.
Raw API responses
solver
{
"reasoning": "CST-1 is the C. elegans ortholog of mammalian STE20-like kinase (MST1/2), the core kinase of the Hippo signaling pathway. As a serine/threonine protein kinase, CST-1 phosphorylates and activates DAF-16 (FOXO transcription factor) directly, independently of the canonical insulin/IGF-1 signaling pathway. Activation of DAF-16 by CST-1 promotes expression of stress-resistance and longevity genes, and overexpression of cst-1 has been shown to extend lifespan in C. elegans. This places CST-1 as a positive regulator of the FOXO/DAF-16 axis, a central node in nutrient-sensing and longevity regulation. The kinase activity and ATP-binding function are the molecular basis for this phosphorylation-driven pro-longevity signaling.",
"confidence": 0.82,
"key_pathways": [
"Hippo signaling / MST1-2 kinase cascade",
"DAF-16/FOXO transcription factor activation",
"Insulin/IGF-1 signaling pathway (parallel axis)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted cst-1 as pro_longevity with high confidence (0.82). The mechanistic reasoning is accurate: CST-1 is indeed the C. elegans ortholog of MST1/2 (mammalian STE20-like kinase), a core Hippo pathway kinase that directly phosphorylates and activates DAF-16/FOXO independently of the canonical IIS pathway, thereby promoting longevity. The model correctly identifies overexpression of cst-1 as extending lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is a reasonable categorization given the DAF-16/FOXO connection, though \"stress_response\" or \"Hippo signaling\" might be more precise. Overall, the prediction and reasoning are well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}