Exp Mol Med.  2002 Mar;34(1):32-37.

D4-GDI is cleaved by caspase-3 during daunorubicin-induced apoptosis in HL-60 cells

• Kwon KB
• Park EK
• Ryu DG
• Park BH

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

Antineoplastic Agents/pharmacology
Apoptosis/drug effects/*physiology
Caspases/antagonists & inhibitors/*metabolism
Cysteine Proteinase Inhibitors/pharmacology
DNA Fragmentation
Daunorubicin/*pharmacology
Dose-Response Relationship, Drug
Enzyme Activation
Guanine Nucleotide Dissociation Inhibitors/*metabolism
HL-60 Cells
Human
Oligopeptides/pharmacology
rho GTP-Binding Proteins/metabolism