Molecular Characterization of Ring Finger Protein 11
Bibliographic record
Abstract
Ring finger proteins serve many vital functions within the cell. We have identified RNF11, a novel 154-amino acid ring finger-containing protein, which is elevated in breast cancer. Within its ring finger domain, RNF11 contains an AKT phosphorylation site (T135) that is situated within a 14-3-3 binding domain. In WM239 cells with constitutively active AKT, RNF11 exhibits seven distinct phosphopeptides as measured using two-dimensional phosphopeptide mapping. Upon inhibition of the AKT pathway or mutation of T135, the phosphorylation at one of these sites is virtually eliminated, suggesting that AKT may phosphorylate RNF11 at T135. Moreover, RNF11 is phosphorylated by AKT in vitro and is recognized by phospho-AKT substrate antibodies. RNF11 shows enhanced binding to 14-3-3 in WM239 cells compared with that seen in the parental WM35 cells which have low AKT activity. Furthermore, treatment of WM239 cells with LY294002 reduces RNF11/14-3-3 interactions suggesting that RNF11/14-3-3 binding is regulated by AKT. In addition, RNF11/14-3-3 binding is enhanced by constitutively active AKT and is diminished by dominant-negative AKT. There is also reduced 14-3-3 binding to T135E RNF11. RNF11 localization was altered from the cytoplasm to the nucleus by activated AKT. Thus, phosphorylation of RNF11 by AKT either causes its nuclear localization or induces degradation of cytoplasmic RNF11. In addition, T135E RNF11, which does not bind 14-3-3 and is not phosphorylated by AKT, causes a greater enhancement of transforming growth factor-beta signaling than wild-type RNF11. It is clear that RNF11 function, localization, and potentially, degradation are regulated by AKT. Disregulation of proper RNF11 function by AKT may prove to be detrimental to patient outcomes, making RNF11 a potential target for novel cancer therapeutics.
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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) | 0.000 | 0.000 |
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".