Silencing an inhibitor unleashes a cytotoxic enzyme.
The ribonuclease inhibitor (RI) is a cytosolic protein and a potent inhibitor of bovine pancreatic ribonuclease (RNase A). Amphibian homologues and variants of RNase A that evade RI are cytotoxic. Here, we employ RNA interference along with amphibian and mammalian ribonucleases to demonstrate that RI protects cells against exogenous ribonucleases. These data indicate an imperative for the molecular evolution of RI and suggest a means of enhancing the cytotoxicity of mammalian ribonucleases.
Dickson
Kimberly A
KA
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706-1544, USA.
Raines
Ronald T
RT
D000818:Animals; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020014:K562 Cells; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D034622:RNA Interference; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C066953:ribonuclease inhibitor, porcine; D012259:Ribonuclease, Pancreatic