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Failure to activate interleukin 1β‐converting enzyme‐like proteases and to cleave retinoblastoma protein in drug‐resistant cells
Author(s) -
An Bing,
Jin Jia-Rui,
Lin Peggy,
Dou Q.Ping
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01311-7
Subject(s) - proteases , etoposide , cleavage (geology) , protease , chemistry , apoptosis , enzyme , caspase , tetrapeptide , retinoblastoma , microbiology and biotechnology , biochemistry , biology , programmed cell death , peptide , paleontology , chemotherapy , fracture (geology) , gene , genetics
We previously found that retinoblastoma (RB) is cleaved at the initiation of apoptotic execution. Here we report that when an HL‐60 cell line resistant to cytosine arabinoside (Ara‐C) was exposed to this anticancer drug, neither RB cleavage nor apoptosis was detected. Consistent with that, processing of interleukin 1β‐converting enzyme (ICE) and CPP32 (an ICE‐like protease) was also prevented in these cells. In contrast, treatment of the HL‐60‐Ara‐C‐resistant cells with etoposide induced all of these apoptotic events. Furthermore, the etoposide‐induced RB cleavage was inhibited by a specific tetrapeptide ICE‐like inhibitor. Our results demonstrate that activation of the RB cleavage enzyme, an ICE‐like protease, is required for overcoming drug resistance.