ArticleThe FEBS journal2009
Onconase cytotoxicity relies on the distribution of its positive charge.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Onconase Induces Apoptosis in Dabrafenib-Resistant Melanoma Cell Lines Through Dysregulation of ROS Homeostasis, Antioxidant Protein Expression, and Mitochondrial Dynamics.International journal of molecular sciences · 2026Article
- Engineering Human Pancreatic RNase 1 as an Immunotherapeutic Agent for Cancer Therapy Through Computational and Experimental Studies.The protein journal · 2024Article
- Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections.International journal of molecular sciences · 2022Review
- Biological Activities of Secretory RNases: Focus on Their Oligomerization to Design Antitumor Drugs.Frontiers in immunology · 2019Review
- Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases.Frontiers in pharmacology · 2019Review
- Cytosolic Delivery of Proteins by Bioreversible Esterification.Journal of the American Chemical Society · 2017Article
- Boronic Acid for the Traceless Delivery of Proteins into Cells.ACS chemical biology · 2016Article
- Sialyl-glycoconjugates in cholesterol-rich microdomains of P388 cells are the triggers for apoptosis induced by Rana catesbeiana oocyte ribonuclease.Glycoconjugate journal · 2014Article
- Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge.Oncoscience · 2014Article
- Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes.Biochemistry · 2013Article
- Fluorogenic probe for constitutive cellular endocytosis.Chemistry & biology · 2013Article
- Urea's effect on the ribonuclease A catalytic efficiency: a kinetic, 1H NMR and molecular orbital study.The protein journal · 2013Article
- Cellular uptake mechanisms and endosomal trafficking of supercharged proteins.Chemistry & biology · 2012Article
- Engineering and identifying supercharged proteins for macromolecule delivery into mammalian cells.Methods in enzymology · 2012Article
- Trimethyl lock: A trigger for molecular release in chemistry, biology, and pharmacology.Chemical science · 2012Article
- Rational design and evaluation of mammalian ribonuclease cytotoxins.Methods in enzymology · 2012Article
- Arginine residues are more effective than lysine residues in eliciting the cellular uptake of onconase.Biochemistry · 2011Article
- Article
- Site-specific folate conjugation to a cytotoxic protein.Bioorganic & medicinal chemistry letters · 2011Article
- Site-specific PEGylation endows a mammalian ribonuclease with antitumor activity.Cancer biology & therapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Onconase (ONC) is a member of the ribonuclease A superfamily that is toxic to cancer cells in vitro and in vivo. ONC is now in Phase IIIb clinical trials for the treatment of malignant mesothelioma. Internalization of ONC to the cytosol of cancer cells is essential for its cytotoxic activity, despite the apparent absence of a cell-surface receptor protein. Endocytosis and cytotoxicity do, however, appear to correlate with the net positive charge of ribonucleases. To dissect the contribution made by the endogenous arginine and lysine residues of ONC to its cytotoxicity, 22 variants were created in which cationic residues were replaced with alanine. Variants with the same net charge (+2 to +5) as well as equivalent catalytic activity and conformational stability were found to exhibit large (> 10-fold) differences in toxicity for the cells of a human leukemia line. In addition, a more cationic ONC variant could be either much more or much less cytotoxic than a less cationic variant, again depending on the distribution of its cationic residues. The endocytosis of variants with widely divergent cytotoxic activity was quantified by flow cytometry using a small-molecule fluorogenic label, and was found to vary by twofold or less. This small difference in endocytosis did not account for the large difference in cytotoxicity, implicating the distribution of cationic residues as being critical for lipid-bilayer translocation subsequent to endocytosis. This finding has fundamental implications for understanding the interaction of ribonucleases and other proteins with mammalian cells.
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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.