Kwon Kang-Beom, Park Eun-Kyung, Ryu Do-Gon, Park Byung-Hyun
Department of Physiology, School of Oriental Medicine, Won-Kwang University, Chonbuk, Korea.
Exp Mol Med. 2002 Mar 31;34(1):32-7. doi: 10.1038/emm.2002.5.
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.
柔红霉素是一种抗癌药物，已知其通过激活半胱天冬酶 - 3（CPP32）以剂量依赖的方式诱导HL - 60细胞凋亡。半胱天冬酶 - 3选择性抑制剂Ac - DEVD - CHO可阻止半胱天冬酶 - 3的激活以及聚（ADP - 核糖）聚合酶（PARP）的裂解。D4 - GDI是造血细胞中Ras相关Rho家族GTP酶的GDP解离抑制剂。在此我们报告D4 - GDI是半胱天冬酶 - 3的底物。在HL - 60细胞中，柔红霉素处理可将D4 - GDI裂解为一个23 kDa的片段，其动力学与细胞凋亡的起始平行。Ac - DEVD - CHO处理可抑制D4 - GDI裂解以及DNA片段化，但半胱天冬酶 - 1抑制剂Ac - YVAD - CHO则无此作用。这些数据表明，Rho家族GTP酶的D4 - GDI可能在细胞凋亡过程中通过半胱天冬酶 - 3介导的GDI蛋白裂解受到调控。
