Cdk4/cyclin D1 kinase, a universal and critical regulator of apoptosis

Kazuhiro Katayama, Yoh Dobashi, Masatoshi Kitagawa, Masataka Kawai, Yuichi Kadoya, Toru Kameya

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)235-243
Number of pages9
JournalAnticancer research
Issue number1 A
Publication statusPublished - 2003 Jan 1


  • Apoptosis
  • Cdk4
  • Cell cycle
  • Cultured cells
  • Cyclin D1
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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