Spy1: A Closer Look at its Binding Mutants
Bibliographic record
Abstract
Breast cancer is the second leading cause of death from cancer among Canadian women, taking the lives of fourteen women each day in Canada. Spy1 (SPEEDY; RINGO) has been previously identified as a novel cell-cycle regulator that is elevated in many breast cancer patients, promoting progression through the cell-cycle and increased cell proliferation. Spy1 is an atypical, cyclin-like protein that is capable of binding directly to Cdk1 and Cdk2, activating their kinase activity to override cell-cycle checkpoints. Spy1 can also promote the degradation of p27, a Cdk inhibitor, through its phosphorylation and binding with Spy1. The mechanism by which Spy1 activates Cdks has been resolved using only Cdk2 and Spy1A, a single member within the Spy1 family. Mutation of D90 reduces binding to Cdk2, whereas the mutation of D97 and E135 on Spy1A were shown to impair the ability of Spy1 to activate Cdk2. Mutating the residues R170/174 and R179/180 reduced its binding with p27, leading to increased p27 expression. There is interest in determining whether these residues are conserved across Spy1 family members and further resolving the impact these mutations have on Spy1 function. We expressed these mutants in HEK-293 cells in the presence and absence of p27 to examine the effects of these mutants on cell growth and binding to its effectors. To investigate sequence homology between the different Spy1 family members, their amino acid sequences were aligned and compared using Basic Local Alignment Search Tool (BLAST). Future work can be done to examine whether the function of these sites is conserved across the family members. Given the involvement of Spy1 in many types of cancer, including more aggressive forms like triple negative breast cancer, the fulfillment of these objectives will provide a better understanding of the protein and the potential for it to be targeted in anti-cancer therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".