Caspase-7 mediated cleavage of proteasome subunits during apoptosis = 세포사멸과정 동안의 caspase-7에 의한 프로테아좀 구성체들의 cleavage

Abstract

Caspase-3 and caspase-7 are structurally closely related and demonstrate overlapping substrate specificity. However, during apoptosis, they are differentially regulated and show distinct subcellular localizations, implying the presence of specific substrates. In this study, to identify caspase-7 substrates, we treated the lysates derived from caspase-3-deficient MCF-7 cells with purified caspase-7 and analyzed decreased proteins by 2-DE. Intriguingly, several proteasome subunits such as α2, α6, and Rpt1 are degraded by caspase-7 during apoptosis in vitro and in vivo. Caspase-7 mediated cleavage of proteasome subunits results in the reduction of proteasome activity and thereby increases the accumulation of ubiquitinated proteins in cells. These findings suggest that caspase-7 facilitates the execution of apoptosis through down-regulation of the 26S proteasome, which regulates the turnover of proteins involved in the apoptotic process.