Failure to activate interleukin 1β‐converting enzyme‐like proteases and to cleave retinoblastoma protein in drug‐resistant cells

FEBS Letters

An, Bing¹  Lin, Peggy¹  Dou, Q.Ping¹  Jin, Jia-Rui¹ 

[1] Department of Pharmacology, University of Pittsburgh School of Medicine, USA

关键词: Apoptosis;    Cancer;    Cleavage;    Drug resistance;    Interleukin 1β-converting enzyme;    Retinoblastoma;   

DOI  :  10.1016/S0014-5793(96)01311-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown