title: SKP1-CULLIN1-F-box (SCF)-mediated DRG2 degradation facilitated chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells.
abstract: 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.
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Bai-Yong
authors.initials: BY
authors.lastname: Shen
authors.forename: Xia-Xing
authors.initials: XX
authors.lastname: Deng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D019204:GTP-Binding Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C100318:Cullin 1; D044842:Cullin Proteins; C409877:DRG2 protein, human; D004317:Doxorubicin; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins