Abstract
The human leukemia cell lines K562, CEM, CEM/VLB(100), human leukemic blasts, and the bladder cancer J82 cell line have different sensitivities to UV light-induced apoptosis. It is reported that resistance to UV light-induced apoptosis occurs at a point in the apoptotic pathway upstream of caspase-3 but downstream of mitochondrial cytochrome c release. It is demonstrated that the block is due to deficiency of Apaf-1, a critical member of the apoptosome. Sensitivity to apoptosis was independent of caspase-9b or XIAP (inhibitors of apoptosis proteins) expression or levels of procaspase-9. Transfection of Apaf-1 conferred sensitivity to apoptosis in resistant cells. Apaf-1 deficiency may constitute a significant mode of resistance to apoptosis in human leukemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / pharmacology
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Apoptosis* / drug effects
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Apoptotic Protease-Activating Factor 1
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Caspase 3
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Caspase 9
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Caspases / analysis
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Caspases / metabolism
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Cytochrome c Group / metabolism*
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Cytochrome c Group / pharmacology
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Enzyme Activation / drug effects
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Granzymes
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Humans
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Leukemia, Myeloid, Acute
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Leukemia-Lymphoma, Adult T-Cell
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Protein Precursors / metabolism
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Proteins / analysis*
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Proteins / genetics
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Proteins / immunology
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Proteins / metabolism
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Serine Endopeptidases / pharmacology
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Transfection
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Tumor Cells, Cultured
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Ultraviolet Rays
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Urinary Bladder Neoplasms
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X-Linked Inhibitor of Apoptosis Protein
Substances
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APAF1 protein, human
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Antibodies
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Apoptotic Protease-Activating Factor 1
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Cytochrome c Group
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Protein Precursors
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Proteins
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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GZMB protein, human
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Granzymes
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Serine Endopeptidases
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CASP3 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 9
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Caspases