title: The role of CDK1 in apoptin-induced apoptosis in hepatocellular carcinoma cells.
abstract: Apoptin, a small protein derived from the chicken anemia virus, specifically induces apoptosis in transformed cells or tumor cells but not in normal cells. Thus, apoptin is involved in a general, tumor-specific pathway. Apoptin-induced apoptosis presumably requires additional interaction partners that activate specific signaling pathways in cancer cells. A number of molecules interact with apoptin and play an important role in the nuclear localization of apoptin or its tumor-selective cytotoxicity. Our data indicated that apoptin selectively kills HepG2 hepatocellular carcinoma (HCC) cells but has no effect on the normal liver cell line HL-7702. Analyses of human HCC tissue samples confirmed that CDK1 (cyclin-dependent kinase 1) activity was detected in primary malignancies but not in healthy paraneoplastic tissues. shRNA knockdown of CDK1 significantly reduced the tumor-specific killing effects of apoptin, suggesting that CDK1 plays an important role in the regulation of apoptin-induced apoptosis. Furthermore, the majority of apoptin translocated to the cytoplasm from the nucleus after knockdown of CDK1. Collectively, our results revealed for the first time that apoptin interacts with CDK1 in the complex process of tumorigenesis. The link between CDK1 and apoptin may be a novel cellular signaling pathway to modulate apoptosis in cancer; therefore, apoptin may have pharmacological potential to be directly employed for cancer therapy.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University Medical college, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Han
authors.forename: Jin-Lu
authors.initials: JL
authors.lastname: Ma
authors.forename: Xia
authors.initials: X
authors.lastname: Ying
authors.forename: Peijun
authors.initials: P
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiguang
authors.initials: J
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D036022:Capsid Proteins; D034741:RNA, Small Interfering; C091717:VP3 protein, Chicken anemia virus; D016203:CDC2 Protein Kinase