Shedding of GPP130 by PC7 and Furin: Potential Implication in Lung Cancer Progression
Bibliographic record
Abstract
From a previously performed proteomics screen, GPP130, or Golgi phosphoprotein of 130 kDa, was identified as a potential substrate of the proprotein convertase 7 (PC7; PCSK7). GPP130 is a type-II transmembrane protein with a luminal domain containing endosomal and Golgi-retrieval determinants, enabling a unique trafficking route. Most of the previous work on GPP130 relates to its binding and retrograde trafficking of the Shiga toxin. However, its cellular biology and its biochemical characterization remain understudied. Recently, GPP130 was reported to be implicated in cell cycle progression and cell proliferation in head and neck cancer cells. This led us to analyze the cBioPortal for Cancer Genomics, revealing that the GPP130/GOLIM4 gene is amplified in many cancers, including lung, ovarian, and cervical. This observation led us to use the A549 lung cancer cell line to investigate the growth-regulating roles of endogenous and overexpressed GPP130 and to analyze the impact of its cleavage/shedding by PC7 and/or Furin on cellular growth. Our cell-based assays suggest that GPP130 is a novel pro-protein convertase substrate that increases cell proliferation in A549, SKOV3, and HeLa cells, and that the latter activity is enhanced following its cleavage by PC7 and/or Furin into a membrane-bound N-terminal product and secreted C-terminal fragments. This novel work sheds light on the cell biology of the poorly characterized GPP130, its proliferative activity, and modulation upon its shedding by PC7 and Furin in lung cancer progression.
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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) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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 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".