Proteases are known to be involved in the apoptotic pathway. We report here that benzyloxycarbonyl(Z)-Leu-Leu-leucinal (ZLLLal), a leupeptin analogue, can induce apoptosis in MOLT-4 and L5178Y cells. ZLLLal is a cell-permeant inhibitor of proteasome. Among the protease inhibitors tested, only calpain inhibitor I (acetyl-Leu-Leu-norleucinal) and ZLLLal caused a marked induction of apoptosis in MOLT-4 cells. In contrast, Z-Leu-leucinal, a specific inhibitor of calpain, did not induce apoptosis. When MOLT-4 cells were incubated in the presence of ZLLLal, p53 accumulated in the cells. These results strongly suggest that inhibition of proteasome induces p53-dependent apoptosis and that proteasome can protect cells from apoptosis.
Apoptosis induction resulting from proteasome inhibition
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Kunio SHINOHARA, Masanori TOMIOKA, Hisako NAKANO, Shigenobu TONÉ, Hisashi ITO, Seiichi KAWASHIMA; Apoptosis induction resulting from proteasome inhibition. Biochem J 15 July 1996; 317 (2): 385–388. doi: https://doi.org/10.1042/bj3170385
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