Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support

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

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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 p16INK4, 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.

Original languageEnglish
Pages (from-to)382-388
Number of pages7
JournalFEBS Letters
Issue number3
Publication statusPublished - 2001 Dec 14
Externally publishedYes


  • Apoptosis
  • Cdk inhibitor
  • Cdk4
  • Cyclin D1
  • Dominant negative cdk4
  • PC12 cell

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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