cul-1
C. elegans
Cullin-1
What the model saw
Gene: cul-1 Organism: Caenorhabditis elegans Known functions: Cullin-1. ubiquitin ligase complex scaffold activity. ubiquitin protein ligase binding.
View unredacted entry
Cullin-1. ubiquitin ligase complex scaffold activity. ubiquitin protein ligase binding.
Solver output
CUL-1 is the C. elegans ortholog of Cullin-1, the scaffold subunit of SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complexes. In C. elegans, CUL-1/SCF complexes are required for ubiquitin-mediated degradation of key cell cycle and signaling regulators, most notably targeting DAF-16 (FOXO transcription factor) inhibitors and components of the DAF-2/insulin-IGF-1 signaling pathway for proteasomal degradation. Loss of cul-1 function impairs proteostasis and cell cycle progression, but critically, CUL-1-dependent SCF complexes also ubiquitinate and degrade negative regulators of DAF-16, thereby promoting DAF-16 nuclear localization and transcriptional activity, which is a well-established pro-longevity axis. Additionally, proper SCF-mediated proteolysis is essential for maintaining proteostasis and preventing accumulation of damaged or misfolded proteins. The net effect of normal CUL-1 function in supporting regulated protein turnover through the ubiquitin-proteasome system is consistent with pro-longevity outcomes in C. elegans.
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 predicts cul-1 as pro_longevity, but the mechanistic reasoning is questionable and likely fabricated. The model claims CUL-1/SCF complexes ubiquitinate and degrade "negative regulators of DAF-16," thereby promoting DAF-16 nuclear localization — this is a speculative and likely incorrect mechanistic claim. In reality, CUL-1 in C. elegans is known to be pro-longevity primarily because it targets cell cycle regulators (like CKI-1/p27) and other substrates for degradation, and loss-of-function of cul-1 causes developmental arrest. The connection to DAF-16/FOXO promotion via degrading DAF-16 inhibitors is not well-established and appears to be confabulated reasoning. The model also misclassifies the mechanism as "deregulated_nutrient_sensing" when the actual mechanism is more related to ubiquitin-proteasome system and cell cycle regulation. The reasoning is internally plausible-sounding but mechanistically dubious.
Raw API responses
solver
{
"reasoning": "CUL-1 is the C. elegans ortholog of Cullin-1, the scaffold subunit of SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complexes. In C. elegans, CUL-1/SCF complexes are required for ubiquitin-mediated degradation of key cell cycle and signaling regulators, most notably targeting DAF-16 (FOXO transcription factor) inhibitors and components of the DAF-2/insulin-IGF-1 signaling pathway for proteasomal degradation. Loss of cul-1 function impairs proteostasis and cell cycle progression, but critically, CUL-1-dependent SCF complexes also ubiquitinate and degrade negative regulators of DAF-16, thereby promoting DAF-16 nuclear localization and transcriptional activity, which is a well-established pro-longevity axis. Additionally, proper SCF-mediated proteolysis is essential for maintaining proteostasis and preventing accumulation of damaged or misfolded proteins. The net effect of normal CUL-1 function in supporting regulated protein turnover through the ubiquitin-proteasome system is consistent with pro-longevity outcomes in C. elegans.",
"confidence": 0.72,
"key_pathways": [
"SCF E3 ubiquitin ligase complex / ubiquitin-proteasome system",
"DAF-2/insulin-IGF-1 signaling and DAF-16/FOXO regulation",
"proteostasis maintenance via targeted protein degradation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicts cul-1 as pro_longevity, but the mechanistic reasoning is questionable and likely fabricated. The model claims CUL-1/SCF complexes ubiquitinate and degrade \"negative regulators of DAF-16,\" thereby promoting DAF-16 nuclear localization — this is a speculative and likely incorrect mechanistic claim. In reality, CUL-1 in C. elegans is known to be pro-longevity primarily because it targets cell cycle regulators (like CKI-1/p27) and other substrates for degradation, and loss-of-function of cul-1 causes developmental arrest. The connection to DAF-16/FOXO promotion via degrading DAF-16 inhibitors is not well-established and appears to be confabulated reasoning. The model also misclassifies the mechanism as \"deregulated_nutrient_sensing\" when the actual mechanism is more related to ubiquitin-proteasome system and cell cycle regulation. The reasoning is internally plausible-sounding but mechanistically dubious.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}