Nuclear Localization and Biological Function of Matrix Metalloproteinase‐2
Bibliographic record
Abstract
Matrix metalloproteinases (MMPs) are zinc‐dependent proteases that are involved in intra‐ and extra‐cellular matrix remodeling associated with developmental processes and disease progression. Several MMPs including MMP‐2 have been found in the nucleus. The biological functions and substrates of nuclear MMPs are mostly unknown. We hypothesize that MMP‐2 is present in the nucleus under physiological conditions but increases during oxidative stress to proteolyse structural and DNA repair proteins. Lamin A/C, a possible nuclear MMP‐2 target, is an intermediate filament protein that provides structural support to the nuclear envelope. Cytosolic, membrane and nuclear fractions were extracted from blood‐free, isolated rat hearts. Western blots for MMP‐2, lamin A/C (nuclear marker), SERCA2 (membrane marker) and GAPDH (cytosol marker) were used to demonstrate fraction purity. This showed that the nuclear fraction was free of cytosolic and membrane contamination and MMP‐2 was detected in all three fractions. MMP‐2 activity (by gelatin zymography) showed that nuclear MMP‐2 activity was lowest compared to that in the cytosolic and membrane fractions. The presence of nuclear MMP‐2 was examined by immunofluorescence confocal microscopy in HT1080 fibrosarcoma cells. Recombinant lamin A/C was proteolysed into 50 and 25 kDa fragments by incubation with MMP‐2 (0.5h, 37 o C) in vitro and this was blocked by the MMP inhibitor o‐phenanthroline. MMP‐2 is present in highly purified nuclear fractions obtained from rat hearts and in the nuclei of HT1080 cells. Ongoing experiments will determine the colocalization of MMP‐2 with nuclear bodies, its nuclear substrates and therefore its function within nuclei. Support: CIHR.
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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".