lin-23
C. elegans
F-box domain-containing protein;F-box/WD repeat-containing protein lin-23
What the model saw
Gene: lin-23 Organism: Caenorhabditis elegans Known functions: F-box domain-containing protein;F-box/WD repeat-containing protein lin-23. beta-catenin binding. phosphatase binding. protein dimerization activity. ubiquitin-like ligase-substrate adaptor activity.
View unredacted entry
F-box domain-containing protein;F-box/WD repeat-containing protein lin-23. beta-catenin binding. phosphatase binding. protein dimerization activity. ubiquitin-like ligase-substrate adaptor activity.
Solver output
LIN-23 is the C. elegans ortholog of β-TrCP, an F-box/WD40 substrate-recognition subunit of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. Its primary molecular role is to act as a ubiquitin-like ligase-substrate adaptor that binds β-catenin (BAR-1 in C. elegans) and targets it for ubiquitin-mediated proteasomal degradation. By restraining β-catenin levels, LIN-23 suppresses Wnt/β-catenin transcriptional output, which drives cell proliferation and can promote tumor-like overproliferation when uncontrolled. Loss-of-function of lin-23 in C. elegans leads to hyperactivation of Wnt signaling, ectopic cell divisions, and developmental defects consistent with uncontrolled proliferative signaling. Maintaining tight control over β-catenin via SCF-LIN-23 prevents aberrant proliferation and supports normal tissue homeostasis, which is broadly associated with extended healthspan and lifespan. The phosphatase-binding and protein dimerization activities further support its role as a regulatory hub in proteostasis and cell-cycle control pathways.
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 pro_longevity for lin-23. The mechanistic reasoning is sound: LIN-23 as the β-TrCP ortholog in the SCF E3 ubiquitin ligase complex targeting β-catenin for degradation, thereby suppressing Wnt signaling and preventing aberrant proliferation, is well-established biology. The connection to longevity through proteostasis and cell-cycle control is reasonable. The mechanism_class of "cellular_senescence" is a minor imprecision — the primary mechanism is more accurately described as ubiquitin-mediated proteolysis/Wnt signaling suppression rather than cellular senescence per se — but the overall reasoning pathway is correct. Confidence of 0.72 is appropriate given the complexity of the prediction.
Raw API responses
solver
{
"reasoning": "LIN-23 is the C. elegans ortholog of β-TrCP, an F-box/WD40 substrate-recognition subunit of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. Its primary molecular role is to act as a ubiquitin-like ligase-substrate adaptor that binds β-catenin (BAR-1 in C. elegans) and targets it for ubiquitin-mediated proteasomal degradation. By restraining β-catenin levels, LIN-23 suppresses Wnt/β-catenin transcriptional output, which drives cell proliferation and can promote tumor-like overproliferation when uncontrolled. Loss-of-function of lin-23 in C. elegans leads to hyperactivation of Wnt signaling, ectopic cell divisions, and developmental defects consistent with uncontrolled proliferative signaling. Maintaining tight control over β-catenin via SCF-LIN-23 prevents aberrant proliferation and supports normal tissue homeostasis, which is broadly associated with extended healthspan and lifespan. The phosphatase-binding and protein dimerization activities further support its role as a regulatory hub in proteostasis and cell-cycle control pathways.",
"confidence": 0.72,
"key_pathways": [
"SCF E3 ubiquitin ligase / proteasomal degradation of β-catenin",
"Wnt/β-catenin signaling suppression",
"cell cycle and proliferation control"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for lin-23. The mechanistic reasoning is sound: LIN-23 as the β-TrCP ortholog in the SCF E3 ubiquitin ligase complex targeting β-catenin for degradation, thereby suppressing Wnt signaling and preventing aberrant proliferation, is well-established biology. The connection to longevity through proteostasis and cell-cycle control is reasonable. The mechanism_class of \"cellular_senescence\" is a minor imprecision — the primary mechanism is more accurately described as ubiquitin-mediated proteolysis/Wnt signaling suppression rather than cellular senescence per se — but the overall reasoning pathway is correct. Confidence of 0.72 is appropriate given the complexity of the prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}