Abstract #4925: Unique role for the Rb LxCxE binding domain in lung development
Bibliographic record
Abstract
The retinoblastoma tumor suppressor protein (Rb) regulates cell division, death and differentiation. Loss of Rb causes retinoblastoma in humans. Previously we developed a mouse model of retinoblastoma using conditional knockout of Rb because germline Rb deletion is lethal. Rb exon 19 is floxed and retinal-specific deletion is driven by \#945;-Cre (\#945;-CreRbf/f). The developing Rb null retina (\#945;-CreRbf/f) shows ectopic cell division and death of certain neurons in the developing retina. Loss of both Rb and its relative p107 (\#945;-CreRbf/f;p107-/-) lead to more extensive ectopic division and additional phenotypes of cone death and tumorigenesis. Rb binds E2f transcription factors and regulates their activity. While bound to E2fs, Rb can also recruit corepressors, many of which have a unique LxCxE motif (L-Leucine, C-Cysteine, E-Glutamate, and X-any amino acid) which binds the LxCxE-binding domain (LBD) of Rb. The role of LxCxE-motif proteins (LMPs) corepressors in mediating Rb function in vivo is unknown. We hypothesized that they may be critical for only a subset of Rb activities. Thus, we used mice with a defective LBD (Rb\#916;), which cannot bind most LMPs, to define LxCxE-corepressor-dependent Rb activities in the retina. One (\#945;-CreRbf/\#916; ) or two (Rb\#916;/\#916;) Rb\#916; alleles suppressed the ectopic division and neuronal apoptosis seen in the Rb null (\#945;-CreRbf/f) retina, although low levels of apoptosis were detected at post natal day 18 (P18). In the absence of p107 and one Rb\#916; alleles (\#945;-CreRbf/\#916;;p107-/-), abnormal cell division and death were partially and tumorigenesis was completely suppressed. Importantly, Rb\#916;/\#916;;p107-/- mice did not survive beyond P0-P1 because of extensive lung hyperplasia, but did not show ectopic division or death in the retina. Collectively, these data suggest that recruitment of LMP corepressors by Rb is dispensable for promoting cell cycle exit and survival in the retina, but regulates lung development. Acknowledgement: This study was supported by grants from CIHR and Foundation Fighting Blindness Canada. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4925.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.004 |
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 source (direct Gemma or distilled Codex), 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".