Determining the Role of Oxysterol Binding Protein‐Related Protein 4 (ORP4) in Cell Proliferation and Survival
Bibliographic record
Abstract
Oxysterol binding protein (OSBP) and related proteins (ORPs) constitute a 12-member family of mammalian lipid binding proteins with diverse cellular expression, localization and ligands. ORP4 is closely related to OSBP and expressed as short (ORP4S), medium (ORP4M) and long (ORP4L) isoforms as a result of alternate transcription start sites. ORP4 was initially discovered in disseminated tumor cells and considered a potential marker of metastasis. We recently showed that lentiviral short-hairpin RNA silencing of ORP4 induced cell-specific growth arrest or apoptosis. To determine how ORP4 promotes cell proliferation and survival, we identified relevant signaling pathways that are activated upon ORP4 silencing. In HeLa cells, ORP4 silencing was accompanied by elevated expression of p21 and phospho-p53 isoforms as well as cell cycle arrest but not apoptosis. ORP4 silencing also induced growth arrest in HEK 293 cells but triggered apoptosis in non-transformed rat intestinal epithelial cells. A potential role for ORP4L in genomic stability is indicated by its interaction with a component of the Mis18 complex required for centromere organization. Mass spectrometry was used to identify a MAPK phosphorylation site in the C-terminal lipid-binding domain of ORP4L. An ORP4L phospho-mimetic (serine-to-glutamate) MAPK site mutant expressed in HeLa cells was associated with an aggregated vimentin network, which was not observed with the corresponding serine-to-alanine mutant or wild-type ORP4L. These data suggest that ORP4L phosphorylation by MAPK enhances its interaction with the cytoskeleton and/or genomic regulators, ultimately affecting p21/p53-dependent control of cell cycle progression.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".