Cathepsin L inhibition prevents the cleavage of multiple nuclear proteins upon lysis of quiescent human cells

Several studies have indicated a role for cathepsin L (CTSL) proteolytic activity in the nucleus under distinct cellular conditions, including during differentiation, senescence, and quiescence. Here we show that addition of CTSL inhibitors to a cell lysis buffer prevents the cleavage of several nuclear proteins during the lysis of quiescent human cells, including proteins previously thought to have functional relevance in other cell and tissue contexts. These findings suggest that care should be taken to use CTSL inhibitors when lysing cells and tissues containing high levels of CTSL protein to differentiate proteolysis that occurs in vivo versus artifactually in vitro.