SKP1-CULLIN1-F-box (SCF)-mediated DRG2 degradation facilitated chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells

被引:20
作者
Chen Jie [1 ]
Shen Bai-yong [1 ]
Deng Xia-xing [1 ]
Zhan Qian [1 ]
Peng Cheng-hong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Gen Surg, Shanghai, Peoples R China
关键词
DRG2; SKP1-CULLIN1-F-box; Chemotherapeutic drugs; Hepatocellular carcinoma cells; SCF UBIQUITIN LIGASE; GTP-BINDING PROTEINS; F-BOX PROTEINS; BETA-TRCP; COMPLEX; PHOSPHORYLATION; ONCOPROTEIN; PROMOTES; INSIGHTS; CANCER;
D O I
10.1016/j.bbrc.2012.03.058
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved member of the DRG subfamily in the GTP-binding protein, is thought to play an essential role in the control of cell growth and differentiation. However, the role of DRG2 in hepatocellular carcinoma cells is largely unknown. Here, we show that DRG2 is down-regulated during chemotherapeutic drug induced apoptosis in four hepatocellular carcinoma cell lines. We further provided evidence that DRG2 was a substrate of a SKP1-CULLIN1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis. Moreover, over-expression of DRG2 inhibited doxorubicin induced apoptosis in hepatocellular carcinoma cells. Taken together, these results demonstrate that regulated degradation of DRG2 has a role in chemotherapeutic drug induced hepatocellular carcinoma cells apoptosis. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:651 / 655
页数:5
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