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  • Title: Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support.
    Author: Katayama K, Dobashi Y, Kitagawa M, Kamekura S, Kawai M, Kadoya Y, Kameya T.
    Journal: FEBS Lett; 2001 Dec 14; 509(3):382-8. PubMed ID: 11749960.
    Abstract:
    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.
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