A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes.
Reticulocytes, like other cells, selectively degrade certain abnormal proteins by an energy-dependent process. When isolated rabbit reticulocytes incorporate the valine analog 2-amino-3chlorobutyric acid (ClAbu) in place of valine, they produce an abnormal globin that is degraded with a half-life of 15 min. Normal hemoglobin, in contrast, undergoes little or no breakdown within these cells. Cell-free extracts from reticulocytes have been shown to rapidly hydrolyze these abnormal proteins. The degradative system is located in the 100,000 X g supernatant, has a pH optimum of 7.8, and does not appear to be of lysosomal origin. This breakdown of analog-containing protein was stimulated severalfold by ATP, and slightly by ADP. AMP and adenosine-3':5'-cyclic monophosphate had no significant effect on proteolysis. Experiments with ATP analogs suggest that the terminal high energy phosphate is important in the degradative process. Proteolysis in the cell-free system and in intact reticulocytes was inhibited by the same agents (L-l-tosylamido-2-phenyl-ethylchloromethyl ketone, N-alpha-p-tosyl-L-lysine chloromethyl ketone, N-ethylmaleimide, iodoacetamide, and o-phenanthroline). In addition, the relative rates of degradation of several polypeptides in the cell-free extracts paralleled degradatives rates within cells. Thus, a soluble nonlysosomal proteolytic system appears responsible for the energy-dependent degradation of abnormal proteins in reticulocytes.
D000255:Adenosine Triphosphate / Q000097:blood*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002474:Cell-Free System; D005914:Globins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood*; D010455:Peptides / Q000097:blood*; D010618:Phenanthrolines / Q000494:pharmacology; D011480:Protease Inhibitors; D011691:Puromycin; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology / Q000378:metabolism*; D012995:Solubility; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000097:blood
D001798:Blood Proteins; D010455:Peptides; D010618:Phenanthrolines; D011480:Protease Inhibitors; D013439:Sulfhydryl Reagents; D014108:Tosylphenylalanyl Chloromethyl Ketone; D011691:Puromycin; D000255:Adenosine Triphosphate; D005914:Globins; D010447:Peptide Hydrolases; D014633:Valine
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