Mitochondrial targeting of FGF-2 antisense proteins and their function in cancer cell proliferation
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 46, 2005 2864 Mammalian cells have evolved a variety of defence mechanisms to protect the integrity of the mitochondrial and nuclear genomes from oxidative damage. These include several members of the Nudix hydrolase superfamily of enzymes, characterized by a loop-helix-loop nudix motif involved in substrate binding and catalysis. Loss of function of nudix genes such as OGG1, MYH and MTH1 has been implicated in mutagenesis and tumorigenesis of lung, colorectal and liver cancers. The highly conserved FGF-2 antisense gene, fgf-as, encodes a novel nudix motif protein called GFG. We recently showed that rat GFG has anti-mutator activity in vitro, and that GFG expression was down regulated in pituitary, esophageal and endometrial cancer tissues. In the present study we investigated the subcellular localization of alternatively spliced GFG isoforms in rat and human cells. At least 3 GFG isoforms are produced by alternative splicing ([Fig 1][1]). The largest isoform contains a putative mitochondrial targetting signal peptide (MTSP) in the N-terminus. To confirm mitochondrial targeting of GFG, full-length and truncated rat and human GFG:GFP constructs were generated. Their subcellular localisation in stably transfected C6 glioma cells was monitored with confocal laser scanning microscopy. Our results indicate that GFP fusions of full-length human or rat GFG proteins bearing the predicted MTSP were targeted highly specifically to mitochondria. Furthermore, an N-terminal 75 aa fragment of rat GFG, containing the MTSP, can efficiently direct GFP to mitochondria. Following deletion of the N-terminal MTSP of rat GFG, the GFP fusion protein was localised in cytoplasm and nucleus. Similarly, the GFP fusion protein of human GFG isoform C, which does not contain the putative MTSP, localised exclusively in cytoplasm and nucleus. These observations indicate that selective trafficking of GFG isoforms to different subcellular compartments may be of central importance to the anti-mutator activity in mitochondria and cytoplasm and/or nucleus. The molecular action of GFG in in rat and human cancer cells is currently under investigation. (supported by the CIHR). ![Figure][2] [1]: #F1 [2]: pending:yes
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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) | 0.002 | 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 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".