Evasion of Ribonuclease Inhibitor as a Determinant of Ribonuclease Cytotoxicity
نویسندگان
چکیده
منابع مشابه
Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.
Onconase (ONC) is an amphibian member of the bovine pancreatic ribonuclease (RNase A) superfamily that exhibits innate antitumoral activity. ONC has been granted both orphan-drug and fast-track status by the U.S. Food and Drug Administration for the treatment of malignant mesothelioma, and is poised to become the first chemotherapeutic agent based on a ribonuclease. Investigations into the mech...
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Onconasetrade mark, a homolog of bovine pancreatic ribonuclease A (RNase A) with high conformational stability, is cytotoxic and has efficacy as a cancer chemotherapeutic agent. Unlike wild-type RNase A, the G88R variant is toxic to cancer cells. Here, variants in which disulfide bonds were removed from or added to G88R RNase A were used to probe the relationship between conformational stabilit...
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Bovine seminal ribonuclease (BS-RNase), a dimeric homolog of bovine pancreatic ribonuclease A (RNase A), is toxic to mammalian cells. In contrast to dimeric BS-RNase, a monomeric BS-RNase and RNase A are not cytotoxic and are bound tightly by cytosolic ribonuclease inhibitor. To elucidate the mechanism of ribonuclease cytotoxicity, we constructed a series of hybrid and semisynthetic enzymes and...
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Protein-protein interactions are critical for the function of biological systems. Here, we describe a means to dissect a protein-protein interaction. Our method is based on the in vivo interaction between a target protein and the peptide epitopes derived from its partner. This interaction is detected by using hybrid proteins in which the target protein and peptide epitopes are fused to the DNA-...
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Onconase (ONC) is a homolog of RNase A that is in clinical trials as a cancer chemotherapeutic agent. The toxicity of ONC and RNase A variants relies on their ability to evade the cytosolic ribonuclease inhibitor protein (RI) and degrade cellular RNA. We find that these ribonucleases are more toxic for more rapidly growing cells. The enhanced cytotoxicity does not arise from variation in the en...
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ژورنال
عنوان ژورنال: Current Pharmaceutical Biotechnology
سال: 2008
ISSN: 1389-2010
DOI: 10.2174/138920108784567344