title: Failure to activate interleukin 1beta-converting enzyme-like proteases and to cleave retinoblastoma protein in drug-resistant cells.
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.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15213-2582, USA.
authors.forename: B
authors.initials: B
authors.lastname: An
authors.forename: J R
authors.initials: JR
authors.lastname: Jin
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.forename: Q P
authors.initials: QP
authors.lastname: Dou
mesh_terms: D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003561:Cytarabine / Q000494:pharmacology; D004351:Drug Resistance; D004789:Enzyme Activation; D005047:Etoposide / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D016160:Retinoblastoma Protein; D003561:Cytarabine; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1