Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support

FEBS Letters

Kitagawa, Masatoshi²  Kawai, Masataka³  Dobashi, Yoh³  Kadoya, Yuichi¹  Kameya, Toru³  Kamekura, Soichiro³  Katayama, Kazuhiro³ 

[1] Department of Anatomy, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 228-8555, Japan;Department of Biochemistry 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan;Department of Pathology, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 228-8555, Japan

关键词: Cdk4;    Cyclin D1;    PC12 cell;    Apoptosis;    Cdk inhibitor;    Dominant negative cdk4;    cdk;    cyclin-dependent kinase;    INK4;    inhibitor of kinase 4;    HPV;    human papilloma virus;    cdk4dn;    dominant negative cdk4;    PI;    propidium iodide;    FITC;    fluorescein-isothiocyanate;    HA;    hemagglutinin;    FACS;    fluorescein-activated cell sorter;   

DOI  :  10.1016/S0014-5793(01)03200-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16^INK4, or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.

【 授权许可】

Unknown