ArticleProceedings of the National Academy of Sciences of the United States of America2014
Circulating proteolytic signatures of chemotherapy-induced cell death in humans discovered by N-terminal labeling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review.Molecular diagnosis & therapy · 2024Pooled it
- Prognosis of metastatic renal cell carcinoma with first-line interferon-α therapy in the era of molecular-targeted therapy.Cancer science · 2016Trial
- N-terminome analyses underscore the prevalence of SPPL3-mediated intramembrane proteolysis among Golgi-resident enzymes and its role in Golgi enzyme secretion.Cellular and molecular life sciences : CMLS · 2022Article
- Discovery of a caspase cleavage motif antibody reveals insights into noncanonical inflammasome function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Assessment of Proteolysis by Pyrylium and Other Fluorogenic Reagents.Protein and peptide letters · 2021Article
- Proteomics identifies a convergent innate response to infective endocarditis and extensive proteolysis in vegetation components.JCI insight · 2020Article
- Molecular stratification of idiopathic nephrotic syndrome.Nature reviews. Nephrology · 2019Review
- A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived FromFrontiers in endocrinology · 2019Article
- From Synthesis to Characterization of Site-Selective PEGylated Proteins.Frontiers in pharmacology · 2019Review
- Engineering peptide ligase specificity by proteomic identification of ligation sites.Nature chemical biology · 2018Article
- Targeting the N terminus for site-selective protein modification.Nature chemical biology · 2017Review
- Comparative Analysis of Mitochondrial N-Termini from Mouse, Human, and Yeast.Molecular & cellular proteomics : MCP · 2017Article
- Sharpening Host Defenses during Infection: Proteases Cut to the Chase.Molecular & cellular proteomics : MCP · 2017Review
- Freeze-dried plasma proteins are stable at room temperature for at least 1 year.Clinical proteomics · 2017Article
- A Panel of Protease-Responsive RNA Polymerases Respond to Biochemical Signals by Production of Defined RNA Outputs in Live Cells.Journal of the American Chemical Society · 2015Article
- One-step site-specific modification of native proteins with 2-pyridinecarboxyaldehydes.Nature chemical biology · 2015Article
- In vivo assessment of protease dynamics in cutaneous wound healing by degradomics analysis of porcine wound exudates.Molecular & cellular proteomics : MCP · 2015Article
- Global analysis of cellular proteolysis by selective enzymatic labeling of protein N-termini.Methods in enzymology · 2014Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
It is known that many chemotherapeutics induce cellular apoptosis over hours to days. During apoptosis, numerous cellular proteases are activated, most canonically the caspases. We speculated that detection of proteolytic fragments released from apoptotic cells into the peripheral blood may serve as a unique indicator of chemotherapy-induced cell death. Here we used an enzymatic labeling process to positively enrich free peptide α-amines in the plasma of hematologic malignancy patients soon after beginning treatment. This N-terminomic approach largely avoids interference by high-abundance proteins that complicate traditional plasma proteomic analyses. Significantly, by mass spectrometry methods, we found strong biological signatures of apoptosis directly in the postchemotherapy plasma, including numerous caspase-cleaved peptides as well as relevant peptides from apoptotic and cell-stress proteins second mitochondria-derived activator of caspases, HtrA serine peptidase 2, and activating transcription factor 6. We also treated hematologic cancer cell lines with clinically relevant chemotherapeutics and monitored proteolytic fragments released into the media. Remarkably, many of these peptides coincided with those found in patient samples. Overall, we identified 153 proteolytic peptides in postchemotherapy patient plasma as potential indicators of cellular apoptosis. Through targeted quantitative proteomics, we verified that many of these peptides were indeed increased post- vs. prechemotherapy in additional patients. Our findings reveal that numerous proteolytic fragments are released from dying tumor cells. Monitoring posttreatment proteolysis may lead to a novel class of inexpensive, rapid biomarkers of cell death.
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