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

Diril, M. Kasim ; Ratnacaram, Chandrahas Koumar ; Padmakumar, V. C. ; Du, Tiehua ; Wasser, Martin ; Coppola, Vincenzo ; Tessarollo, Lino and Kaldis, Philipp LU (2012) In Proceedings of the National Academy of Sciences of the United States of America 109(10). p.3826-3831
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Cancer, Cell cycle regulation, Knockout mice, Polyploidy
in
Proceedings of the National Academy of Sciences of the United States of America
volume
109
issue
10
pages
3826 - 3831
publisher
National Acad Sciences
external identifiers
  • scopus:84857956418
  • pmid:22355113
ISSN
0027-8424
DOI
10.1073/pnas.1115201109
language
English
LU publication?
no
id
960af545-f2cb-4891-8d6a-4ccfaccd7b40
date added to LUP
2019-09-18 14:00:10
date last changed
2020-06-03 05:10:13
@article{960af545-f2cb-4891-8d6a-4ccfaccd7b40,
  abstract     = {<p>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.</p>},
  author       = {Diril, M. Kasim and Ratnacaram, Chandrahas Koumar and Padmakumar, V. C. and Du, Tiehua and Wasser, Martin and Coppola, Vincenzo and Tessarollo, Lino and Kaldis, Philipp},
  issn         = {0027-8424},
  language     = {eng},
  month        = {03},
  number       = {10},
  pages        = {3826--3831},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration},
  url          = {http://dx.doi.org/10.1073/pnas.1115201109},
  doi          = {10.1073/pnas.1115201109},
  volume       = {109},
  year         = {2012},
}