Lens proteins are substrates for the reticulocyte ubiquitin conjugation system.

In the aged lens postsynthetically altered molecules comprise the majority of lens proteins. Many proteolytic activities have been observed in lens supernatants. Since damaged or altered proteins are usually selectively and rapidly degraded in other cells and tissues, the accumulation of these species in the lens seemed enigmatic. Initiation of proteolysis has been studied most extensively in reticulocytes and ts 85 cells. In these systems proteolysis is absolutely ATP dependent, occurs effectively on high molecular weight substrates and, at least for a majority of proteolytic reactions, requires conjugation of ubiquitin to putative substrates. It seemed plausible that the accumulation of high molecular weight protein aggregates in older lenses might be due to the attenuated function of these ubiquitin- and ATP-dependent components in the initial committing processes of proteolysis. This research shows that: ubiquitin is present in the lens; lens proteins are conjugated to 125I-ubiquitin using reticulocyte conjugating systems; the reaction is ATP dependent; proteins from lens epithelium/outer cortex and core form different ubiquitin conjugates; lens proteins compete with lysozyme and reticulocyte proteins for the ubiquitin conjugating apparatus; most of the conjugates are of very high molecular weight; there is a temporal nature to the pattern of conjugates observed; and the ubiquitin conjugation system shows extreme selectivity.