Cdk4/cyclin D1 kinase, a universal and critical regulator of apoptosis.
BACKGROUND
We have previously described that overexpression of cdk4/cyclin D1 is the primary and critical mediator of apoptosis in PC12 cells even under otherwise physiological conditions. However, it is unclear whether this phenomenon is specific to neuronal cells or is more universally true.


METHODS
Cyclins and cdks were transiently overexpressed in a variety of cultured cells, and examined for apoptosis.


RESULTS
By flow cytometry, apoptosis was observed in all cell lines overexpressing cdk4 or cyclin D1. Immunofluorescence revealed that cells overexpressing cdk4 or cyclin D1 exhibited nuclear features characteristic of apoptosis. Furthermore, in cells defective for retinoblastoma protein (Rb), apoptosis could be induced by overexpression of any cdks or cyclins.


CONCLUSIONS
Up-regulation of cdk4 kinase activity is the primary and critical mediator of apoptosis regardless of the cell types. In addition, inactivation of Rb renders cells further susceptible to apoptosis by abnormal expression of any of the cell cycle regulators.
Katayama
Kazuhiro
K
Department of Pathology, Kitasato University School of Medicine, Kitasato, Kanagawa 228-8555, Japan.
Dobashi
Yoh
Y
Kitagawa
Masatoshi
M
Kawai
Masataka
M
Kadoya
Yuichi
Y
Kameya
Toru
T
D017209:Apoptosis / Q000502:physiology*; D019938:Cyclin D1 / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000502:physiology; D020298:U937 Cells
D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases