ArticleProceedings of the National Academy of Sciences of the United States of America1998
Ribonuclease A variants with potent cytotoxic activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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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
73 citing papers in PubMed, 219 citations in OpenAlex.
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- The role of angiogenin in bladder cancer: where are we in 2025?International urology and nephrology · 2025Review
- Intracellular Delivery of Native Proteins by BioReversible Arginine Modification (BioRAM) on Amino Groups.Angewandte Chemie (International ed. in English) · 2025Article
- Ribonuclease 1 Induces T-Cell Dysfunction and Impairs CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ribonucleases of Mice and Men: Unveiling the Roles of the RNase A Superfamily in Host Defence.Journal of immunology research · 2025Review
- Engineering Human Pancreatic RNase 1 as an Immunotherapeutic Agent for Cancer Therapy Through Computational and Experimental Studies.The protein journal · 2024Article
- Robust Recombinant Expression of Human Placental Ribonuclease Inhibitor in Insect Cells.Biomolecules · 2022Article
- Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection.AIDS research and therapy · 2021Article
- Impedance analysis of adherent cells after in situ electroporation-mediated delivery of bioactive proteins, DNA and nanoparticles in µL-volumes.Scientific reports · 2020Article
- Magnetite Nanoparticles Functionalized with RNases against Intracellular Infection ofPharmaceutics · 2020Article
- RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue.Frontiers in physiology · 2020Article
- Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.Biomedicines · 2018Review
- Nanoparticle core stability and surface functionalization drive the mTOR signaling pathway in hepatocellular cell lines.Scientific reports · 2017Article
- Copper (II) binding of NAD(P)H- flavin oxidoreductase (NfoR) enhances its Cr (VI)-reducing ability.Scientific reports · 2017Article
- One-Pot Synthesis of Multiple Protein-Encapsulated DNA Flowers and Their Application in Intracellular Protein Delivery.Advanced materials (Deerfield Beach, Fla.) · 2017Article
- Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase.Oncotarget · 2017Article
- A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells.Oncotarget · 2016Article
- Boronic Acid for the Traceless Delivery of Proteins into Cells.ACS chemical biology · 2016Article
- Human Cancer Antigen Globo H Is a Cell-Surface Ligand for Human Ribonuclease 1.ACS central science · 2015Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Select members of the bovine pancreatic ribonuclease A (RNase A) superfamily are potent cytotoxins. These cytotoxic ribonucleases enter the cytosol, where they degrade cellular RNA and cause cell death. Ribonuclease inhibitor (RI), a cytosolic protein, binds to members of the RNase A superfamily with inhibition constants that span 10 orders of magnitude. Here, we show that the affinity of a ribonuclease for RI plays an integral role in defining the potency of a cytotoxic ribonuclease. RNase A is not cytotoxic and binds RI with high affinity. Onconase, a cytotoxic RNase A homolog, binds RI with low affinity. To disrupt the RI-RNase A interaction, three RNase A residues (Asp-38, Gly-88, and Ala-109) that form multiple contacts with RI were replaced with arginine. Replacing Asp-38 and Ala-109 with an arginine residue has no effect on the RI-RNase interaction. In addition, these variants are not cytotoxic. In contrast, replacing Gly-88 with an arginine residue yields a ribonuclease (G88R RNase A) that retains catalytic activity in the presence of RI and is cytotoxic to a transformed cell line. Replacing Gly-88 with aspartate also yields a ribonuclease (G88D RNase A) with a decreased affinity for RI and cytotoxic activity. The cytotoxic potency of onconase, G88R RNase A, and G88D RNase A correlate with RI evasion. We conclude that ribonucleases that retain catalytic activity in the presence of RI are cytotoxins. This finding portends the development of a class of chemotherapeutic agents based on pancreatic ribonucleases.
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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.