Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration

Research output: Contribution to journalArticle

Abstract

Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.

Details

Authors
  • M. Kasim Diril
  • Chandrahas Koumar Ratnacaram
  • V. C. Padmakumar
  • Tiehua Du
  • Martin Wasser
  • Vincenzo Coppola
  • Lino Tessarollo
  • Philipp Kaldis
External organisations
  • National University of Singapore
  • Ohio State University
  • A*Star Institute of Molecular and Cell Biology (IMCB)
  • National Cancer Institute at Frederick
  • A*Star, Bioinformatics Institute (BII)
Research areas and keywords

Keywords

  • Cancer, Cell cycle regulation, Knockout mice, Polyploidy
Original languageEnglish
Pages (from-to)3826-3831
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number10
Publication statusPublished - 2012 Mar 6
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes