Levels of proteolytic activities and cell protein degradation

The chanelling of substrate proteins to the degradative sites is generally considered to be the main limiting step for both basal and accelerated cell protein catabolism. On the other hand, circumstantial evidence from different laboratories suggests that overall protein catabolic rates and intracellular levels of proteolytic activities may be related. Two relevant examples are discussed. The first concerns the effects of repeated doses of cycloheximide on the rat liver, which result in stabilization of slow-turnover proteins concurrent with a marked reduction in lysosomal proteinase activities. The second is liver growth, both developmental and induced, where decreased protein degradation is likewise associated with reduced proteinase activity levels. In the regenerating liver, in particular, the reduction in lysosomal enzyme activities is not homogeneously distributed among cells, but seems mainly accounted for by changes which involve dividing hepatocytes. Evidence is presented indicating that the intracellular level of lysosomal proteinase activities, particularly cathepsin B, in the liver is subjected to relatively rapid adjustments, which is compatible with a possible role for them in the regulation of cell protein catabolism.