ArticleThe Journal of biological chemistry2010
Characterization of the substrate specificity of human carboxypeptidase A4 and implications for a role in extracellular peptide processing.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Limitations of Mass Spectrometry-Based Peptidomic Approaches.Journal of the American Society for Mass Spectrometry · 2015Pooled it
- Review
- CPA4 overexpression correlates with poor prognosis and tumor progression in endometrial cancer.European journal of medical research · 2025Article
- CPA4 as a biomarker promotes the proliferation, migration and metastasis of clear cell renal cell carcinoma cells.Journal of cellular and molecular medicine · 2024Article
- Quantitative Peptidomics: General Considerations.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Comprehensive Analysis of CPA4 as a Poor Prognostic Biomarker Correlated with Immune Cells Infiltration in Bladder Cancer.Biology · 2021Article
- Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis.International journal of molecular sciences · 2021Article
- Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non-small cell lung cancer.Molecular oncology · 2021Article
- Competing Endogenous RNA Networks in Glioma.Frontiers in genetics · 2021Review
- Substrate Specificity and Structural Modeling of Human Carboxypeptidase Z: A Unique Protease with a Frizzled-Like Domain.International journal of molecular sciences · 2020Article
- Transgenerational epigenetic and transcriptomic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rat.Archives of toxicology · 2020Article
- CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling.OncoTargets and therapy · 2020Article
- Identification of potential microRNAs and their targets in promoting gefitinib resistance by integrative network analysis.Journal of thoracic disease · 2019Article
- Downregulation of CPA4 inhibits non small-cell lung cancer growth by suppressing the AKT/c-MYC pathway.Molecular carcinogenesis · 2019Article
- Characterization, Recombinant Production and Structure-Function Analysis of NvCI, A Picomolar Metallocarboxypeptidase Inhibitor from the Marine SnailMarine drugs · 2019Article
- Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma.International journal of experimental pathology · 2019Article
- Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer.International journal of oncology · 2019Article
- Monoclonal antibody AC10364 inhibits cell proliferation in 5-fluorouracil resistant hepatocellular carcinoma via apoptotic pathways.OncoTargets and therapy · 2019Article
- Differential transcriptional changes in human alveolar epithelial A549 cells exposed to airborne PMEnvironmental science and pollution research international · 2018Article
- Emerging challenges in the design of selective substrates, inhibitors and activity-based probes for indistinguishable proteases.The FEBS journal · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
CPA4 (carboxypeptidase A4) is a member of the metallocarboxypeptidase family. CPA4 was originally found in a screen of mRNAs up-regulated by sodium butyrate-induced differentiation of cancer cells. Further studies suggested a relation between CPA4 and prostate cancer aggressiveness. In the present study, we determined that CPA4 is secreted from cells as a soluble proenzyme (pro-CPA4) that can be activated by endoproteases, such as trypsin. Three complementary approaches were used to study the substrate specificity of CPA4; kinetic analysis was performed using a new series of chromogenic substrates and some biologically relevant peptides, the cleavage of synthetic peptides was tested individually, and the cleavage of a mixture of >100 mouse brain peptides was examined using a quantitative peptidomics mass spectrometry-based approach. CPA4 was able to cleave hydrophobic C-terminal residues with a preference for Phe, Leu, Ile, Met, Tyr, and Val. However, not all peptides with C-terminal hydrophobic residues were cleaved, indicating the importance of additional residues within the peptide. Aliphatic, aromatic, and basic residues in the P1 position have a positive influence on the cleavage specificity. In contrast, acidic residues, Pro, and Gly have a negative influence in the P1 position. Some of the peptides identified as CPA4 substrates (such as neurotensin, granins, and opioid peptides) have been previously shown to function in cell proliferation and differentiation, potentially explaining the link between CPA4 and cancer aggressiveness. Taken together, these studies suggest that CPA4 functions in neuropeptide processing and regulation in the extracellular environment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.