Cleavage of the amino terminus of the prion protein by reactive oxygen species

J Biol Chem. 2001 Jan 19;276(3):2286-91. doi: 10.1074/jbc.M007243200. Epub 2000 Nov 1.


Relatively limited information is available on the processing and function of the normal cellular prion protein, PrP(C). Here it is reported for the first time that PrP(C) undergoes a site-specific cleavage of the octapeptide repeat region of the amino terminus on exposure to reactive oxygen species. This cleavage was both copper- and pH-dependent and was retarded by the presence of other divalent metal ions. The oxidative state of the cell also decreased detection of full-length PrP(C) and increased detection of amino-terminally fragmented PrP(C) within cells. Such a post-translational modification has vast implications for PrP(C), in its processing, because such cleavage could alter further proteolysis, and in the formation of the scrapie isoform of the prion protein, PrP(Sc), because abnormal cleavage of PrP(Sc) occurs into the octapeptide repeat region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Chelating Agents / metabolism
  • Cricetinae
  • Dimethyl Sulfoxide / metabolism
  • Hydrogen Peroxide / metabolism
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Metals / metabolism
  • Prions / chemistry
  • Prions / metabolism*
  • Reactive Oxygen Species*


  • Chelating Agents
  • Metals
  • Prions
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Dimethyl Sulfoxide