fzy-1
C. elegans
WD repeat-containing protein fzy-1
What the model saw
Gene: fzy-1 Organism: Caenorhabditis elegans Known functions: WD repeat-containing protein fzy-1. anaphase-promoting complex binding. protein binding. ubiquitin ligase activator activity. ubiquitin-protein transferase activator activity.
View unredacted entry
WD repeat-containing protein fzy-1. anaphase-promoting complex binding. protein binding. ubiquitin ligase activator activity. ubiquitin-protein transferase activator activity.
Solver output
fzy-1 encodes the C. elegans homolog of Cdc20/fizzy, a WD40-repeat co-activator of the Anaphase-Promoting Complex/Cyclosome (APC/C). By activating APC/C ubiquitin ligase activity, fzy-1 drives ubiquitin-mediated proteolysis of key mitotic substrates (e.g., cyclin B, securin), enabling proper mitotic exit and chromosome segregation. Accurate chromosome segregation is essential to prevent genomic instability and aneuploidy, which are hallmarks of cellular senescence and aging. Additionally, APC/C-Cdc20 activity in post-mitotic tissues (including neurons) regulates proteostasis by targeting specific substrates for degradation, contributing to protein quality control. Loss of APC/C co-activator function has been linked to accelerated aging phenotypes in model organisms, suggesting that normal fzy-1 function supports longevity by maintaining mitotic fidelity and proteolytic clearance of pro-aging substrates.
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 but the ground truth is anti_longevity. fzy-1 is the C. elegans Cdc20/fizzy homolog that activates the APC/C. The model reasoned that fzy-1 supports longevity by maintaining mitotic fidelity and proteostasis, but the actual finding is that fzy-1 is anti-longevity (meaning its loss or reduction extends lifespan, or its presence shortens it). The model's mechanistic reasoning was speculative and ultimately incorrect - it assumed that because APC/C activity is important for cell division, loss of fzy-1 would be harmful to longevity, but in C. elegans the APC/C-Cdc20 pathway appears to promote aging rather than prevent it. The model showed moderate confidence (0.62) but got both the answer and the mechanism wrong. The mechanism class of "cellular_senescence" is also questionable for C. elegans which doesn't undergo classical cellular senescence.
Raw API responses
solver
{
"reasoning": "fzy-1 encodes the C. elegans homolog of Cdc20/fizzy, a WD40-repeat co-activator of the Anaphase-Promoting Complex/Cyclosome (APC/C). By activating APC/C ubiquitin ligase activity, fzy-1 drives ubiquitin-mediated proteolysis of key mitotic substrates (e.g., cyclin B, securin), enabling proper mitotic exit and chromosome segregation. Accurate chromosome segregation is essential to prevent genomic instability and aneuploidy, which are hallmarks of cellular senescence and aging. Additionally, APC/C-Cdc20 activity in post-mitotic tissues (including neurons) regulates proteostasis by targeting specific substrates for degradation, contributing to protein quality control. Loss of APC/C co-activator function has been linked to accelerated aging phenotypes in model organisms, suggesting that normal fzy-1 function supports longevity by maintaining mitotic fidelity and proteolytic clearance of pro-aging substrates.",
"confidence": 0.62,
"key_pathways": [
"APC/C ubiquitin ligase activation",
"mitotic exit and chromosome segregation",
"ubiquitin-mediated proteolysis"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. fzy-1 is the C. elegans Cdc20/fizzy homolog that activates the APC/C. The model reasoned that fzy-1 supports longevity by maintaining mitotic fidelity and proteostasis, but the actual finding is that fzy-1 is anti-longevity (meaning its loss or reduction extends lifespan, or its presence shortens it). The model's mechanistic reasoning was speculative and ultimately incorrect - it assumed that because APC/C activity is important for cell division, loss of fzy-1 would be harmful to longevity, but in C. elegans the APC/C-Cdc20 pathway appears to promote aging rather than prevent it. The model showed moderate confidence (0.62) but got both the answer and the mechanism wrong. The mechanism class of \"cellular_senescence\" is also questionable for C. elegans which doesn't undergo classical cellular senescence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}