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

FEBS Letters
B AnQ P Dou

Abstract

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 1beta-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.

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q P DouP L Will
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Citations

Sep 24, 1999·Journal of Neuroscience Research·S L Chan, M P Mattson
Sep 24, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A S Lundberg, R A Weinberg
Mar 11, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A S Lundberg, R A Weinberg
Aug 15, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·M T Jennings, S Iyengar
May 28, 1998·The Journal of Biological Chemistry·M F SantoroD A Giegel
Aug 28, 1998·Science·G Evan, T Littlewood

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