Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support.
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.
Katayama
K
K
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Dobashi
Y
Y
Kitagawa
M
M
Kamekura
S
S
Kawai
M
M
Kadoya
Y
Y
Kameya
T
T
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D048429:Cell Size; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D016193:G1 Phase; D015870:Gene Expression; D005799:Genes, Dominant; D009154:Mutation; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins; D051381:Rats; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine; D016650:Fluorescein-5-isothiocyanate