A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes.

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Abstract
When isolated rabbit reticulocytes incorporate the valine analog 2-amino-3-chlorobutyric acid (ClAbu) in place of valine, they produce an abnormal globin that is degraded with a half-life of 15 min. Normal Hb, in contrast, undergoes little or no breakdown within these cells. Cell-free extracts from reticulocytes rapidly hydrolyze these abnormal proteins. The degradative system is located in the 100,000 .times. 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 cyclic AMP 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-1-tosylamido-2-phenylethylchloromethyl ketone, N-.alpha.-p-tosyl-L-lysine chloromethyl ketone, N-ethylmaleimide, iodoacetamide and o-phenanthroline). The relative rates of degradation of several polypeptides in the cell-free extracts paralleled degradative rates within cells. A soluble nonlysosomal proteolytic system appears responsible for the energy-dependent degradation of abnormal proteins in reticulocytes.