title: A mechanism for accelerated degradation of intracellular proteins after limited damage by free radicals.
abstract: I propose that limited free radical attack upon proteins, occurring continuously in cells, creates new N-termini (notably aspartate and glutamate) which render the proteins more susceptible to proteolysis by the ubiquitin conjugation system. I suggest that these reactions are a significant part of the previously described 'N-end' and 'PEST' rules, which indicate amino acid termini or sequences which tend to dictate short protein half-lives. I also argue that the N-end rule may apply to sequestered intracellular sites, such as mitochondria, these also being sites of radical generation.
mesh_terms: D000595:Amino Acid Sequence; D005609:Free Radicals; D008962:Models, Theoretical; D010447:Peptide Hydrolases / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014452:Ubiquitins / Q000502:physiology
chemical_list: D005609:Free Radicals; D011506:Proteins; D014452:Ubiquitins; D010447:Peptide Hydrolases