Silencing an inhibitor unleashes a cytotoxic enzyme

Biochemistry. 2009 Jun 16;48(23):5051-3. doi: 10.1021/bi900489y.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cytosol / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • K562 Cells
  • Models, Molecular
  • Protein Conformation
  • Proteins / chemistry
  • RNA Interference*
  • Ribonuclease, Pancreatic / antagonists & inhibitors
  • Ribonuclease, Pancreatic / chemistry*
  • Ribonuclease, Pancreatic / toxicity


  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • ribonuclease inhibitor, porcine
  • Ribonuclease, Pancreatic