Abstract
Daunorubicin, an anti-cancer drug, is known to induce apoptosis in HL-60 cells in a dose-dependent manner through the activation of caspase-3 (CPP32). Caspase-3 selective inhibitor, Ac-DEVD-CHO, prevented both the activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). D4-GDI is a GDP dissociation inhibitor for the Ras-related Rho family GTPase in hematopoietic cells. Here we report that D4-GDI is a substrate for the caspase-3. D4-GDI was cleaved to a 23 kDa fragment by daunorubicin treatment in HL-60 cells with kinetics that parallel the onset of apoptosis. D4-GDI cleavage as well as DNA fragmentation was inhibited by treatment with Ac-DEVD-CHO but not with Ac-YVAD-CHO, a caspase-1 inhibitor. These data suggest that D4-GDI of Rho family GTPase may be regulated during apoptosis through the caspase-3 mediated cleavage of the GDI protein.
MeSH terms
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspase 3
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Caspase Inhibitors
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Caspases / metabolism*
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Cysteine Proteinase Inhibitors / pharmacology
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DNA Fragmentation
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Daunorubicin / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme Activation
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Guanine Nucleotide Dissociation Inhibitors / metabolism*
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HL-60 Cells
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Humans
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Oligopeptides / pharmacology
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rho GTP-Binding Proteins / metabolism
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rho Guanine Nucleotide Dissociation Inhibitor beta
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
Substances
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ARHGDIB protein, human
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Antineoplastic Agents
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Caspase Inhibitors
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Cysteine Proteinase Inhibitors
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Guanine Nucleotide Dissociation Inhibitors
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Oligopeptides
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acetyl-aspartyl-glutamyl-valyl-aspartal
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rho Guanine Nucleotide Dissociation Inhibitor beta
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
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CASP3 protein, human
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Caspase 3
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Caspases
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rho GTP-Binding Proteins
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Daunorubicin