title: Survivin deficiency induces apoptosis and cell cycle arrest in HepG2             hepatocellular carcinoma cells.
abstract: The postulated dual roles of survivin as an anti-apoptotic factor and a             mitotic inducer have placed this factor in the spotlight of cancer research. The             purpose of this study was to investigate whether survivin might connect the cell             cycle with apoptosis. Here, by simultaneously monitoring survivin deficiency-induced             morphological changes of HepG2 cells using time-lapse imaging as well as determining             apoptosis progression, we observed synchronized defective mitosis characterized             by multinucleated and polyploid cells and cell cycle arrest at S phase or G2/M             phase followed by apoptosis, the processes of which depended on the simultaneous             destruction of specialized subcellular compartments of survivin and activation             of caspase-3-like protease. These findings showed that the survivin protein acted             as mitotic regulator and apoptosis inhibitor, but may also possess the role of             a bridge in integrating apoptosis and cell division. An essential prerequisite             of this pathway was the specialized subcellular localization of survivin. The             overexpression of survivin was required to maintain cell viability and proper             cell cycle transitions, and to preserve genetic fidelity during cell division             in HepG2 cells.
authors.affiliation: Department of General Surgery, Shanghai Eighth People's Hospital, Jiangshu University, 8 Caobao Road, Shanghai 200235, PR China. daidejian@hotmail.com
authors.forename: Dejian
authors.initials: D
authors.lastname: Dai
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008938:Mitosis / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D011123:Polyploidy; D012333:RNA, Messenger / Q000235:genetics; D000077022:Survivin; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000077022:Survivin; D010447:Peptide Hydrolases; D053148:Caspase 3