Antitumor action of seminal ribonuclease, its dimeric structure, and its resistance to the cytosolic ribonuclease inhibitor.
Bovine seminal RNase (BS-RNase) is a homodimeric enzyme with a cytotoxic activity selective for tumor cells. In this study, the relationships of its cytotoxic activity to its dimeric structure and its resistance to the cytosolic RNase inhibitor (cRI) are investigated systematically by site-directed mutagenesis. The results show that (1) the dimericity of BS-RNase is essential for its full cytotoxic action; (2) the role of the dimeric structure in the antitumor activity is that of making the enzyme insensitive to the cytosolic RNase inhibitor; (3) a RNase may not be completely insensitive to cRI to exploit a full cytotoxic potential.
Antignani
A
A
Department of Organic and Biological Chemistry, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Naddeo
M
M
Cubellis
M V
MV
Russo
A
A
D'Alessio
G
G
D016475:3T3 Cells; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D001120:Arginine / Q000235:genetics; D002417:Cattle; D003600:Cytosol / Q000201:enzymology*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D004351:Drug Resistance; D004722:Endoribonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000235:genetics; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D008239:Lysine / Q000235:genetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity; D012661:Semen / Q000201:enzymology*; D012694:Serine / Q000235:genetics; D014364:Tryptophan / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D011506:Proteins; D011994:Recombinant Proteins; D018698:Glutamic Acid; D012694:Serine; D014364:Tryptophan; D001120:Arginine; D004722:Endoribonucleases; C032523:ribonuclease SPL; D008239:Lysine