title: Cdk4/cyclin D1 kinase, a universal and critical regulator of apoptosis.
abstract: 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.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Kitasato, Kanagawa 228-8555, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Kawai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kadoya
authors.forename: Toru
authors.initials: T
authors.lastname: Kameya
mesh_terms: 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
chemical_list: D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases