title: Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration.
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.
authors.affiliation: Institute of Molecular and Cell Biology,  Agency for Science, Technology, and Research (ASTAR),  Republic of Singapore 138673.
authors.forename: M Kasim
authors.initials: MK
authors.lastname: Diril
authors.forename: Chandrahas Koumar
authors.initials: CK
authors.lastname: Ratnacaram
authors.forename: V C
authors.initials: VC
authors.lastname: Padmakumar
authors.forename: Tiehua
authors.initials: T
authors.lastname: Du
authors.forename: Martin
authors.initials: M
authors.lastname: Wasser
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Coppola
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Philipp
authors.initials: P
authors.lastname: Kaldis
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016158:Genes, p53; D011905:Genes, ras; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D011123:Polyploidy; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase; D018631:ras Proteins